Amide compounds and medications containing the same technical field

ABSTRACT

The present invention provides to a novel compound having an ACAT inhibiting activity. 
     The present invention relates to compounds represented by formula (I) 
                 
         wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group,   Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring,   X represents —NH—, an oxygen atom or a sulfur atom,   Y represents —NR 4 —, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone,   Z represents a single bond or —NR 5 —,   R 4  represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group,   R 5  represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and   n is integer of from 1 to 15,
 
or salts or solvates thereof, and a pharmaceutical composition containing at one of these compounds.

This application is a continuation of Ser. No. 09/358,083 filed Jul. 21, 1999, now abandoned.

TECHNICAL FIELD

The present invention relates to novel amide compounds and medications containing the same. More specifically, the present invention relates to compounds represented by the the formula (I)

-   -   wherein     -   represents an optionally substituted divalent residue such as         benzene, pyridine, cyclohexane or naphthalene, or a group,     -   Het represents a 5- to 8-membered, substituted or unsubstituted         heterocyclic group containing at least one heteroatom selected         from the group consisting of a nitrogen atom, an oxygen atom and         a sulfur atom, such as a monocyclic group, a polycyclic group or         a group of a fused ring,     -   X represents —NH—, an oxygen atom or a sulfur atom,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group, and         n is an integer of from 1 to 15,         or salts or solvates thereof, and a pharmaceutical composition         containing these compounds.

Specifically, the present invention relates to compounds represented by the the formula (IA)

-   -   wherein     -   represents an optionally substituted divalent residue such as         benzen or pyridine,     -   Py represents an optionally substituted pyridyl or pyrimidyl         group,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group, and     -   n is an integer of from 1 to 15,         or salts or solvates thereof, and a pharmaceutical composition         containing these compounds.

More specifically, the present invention relates to compounds represented by the formula (II)

-   -   wherein     -   X represents —NH—, an oxygen atom or a sulfur atom, Y represents         —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   Py represents an optionally substituted pyridyl or pyrimidyl         group, and     -   n is an integer of from 1 to 15,         or salts or solvates thereof, and a pharmaceutical composition         containing these compounds.

BACKGROUND ART

In recent years, hyperlipemia and arteriosclerosis derived therefrom have been rapidly increased with the change to western eating habits with high-calory and high-cholesterol foods bused on the higher level of life and with the advance of age of the population, and this has been one of social problems. The conventional pharmacotherapy of hyperlipemia and arteriosclerosis has mainly put stress on the decrease in blood lipid that causes these diseases, and the lesion of the arteriosclerosis itself has not been treated as a target. Acyl coenzyme A cholesterol acyltransferase (ACAT) is an enzyme that catalyzes synthesis from cholesterol to cholesterol ester, and plays a vital role in metabolism of cholesterol and absorption thereof in digestive organs. Inhibition of the ACAT enzyme that catalyzes esterification of free cholesterol in epithelial cells of the small intestine results in inhibition of absorption of cholesterol from the intestine, and inhibition of synthesis of cholesterol ester in the liver based on the ACAT inhibition results in suppression of secretion of VLDL from the liver to the blood. These results are considered to lead to an activity of decreasing blood cholesterol. Most of conventional ACAT inhibitors have been expected to exhibit an activity of decreasing blood cholesterol as an antihyperlipemic agent by acting on the ACAT enzymes in the small intestine and the liver.

For example, as an ACAT inhibitor, the specification of U.S. Pat. No. 4,716,175 describes 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide, and European Patent No. 372,445 describes N′-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-N-heptylurea. However, most of the conventional ACAT inhibitors have put stress on an activity of decreasing blood cholesterol as an antihyperlipemic agent, and the administration thereof at a high dose for exhibiting its activity has often caused side effects such as intestinal bleeding, intestinal disorders, diarrhea, hepatopathy and the like at the stage of a clinical test, making difficult the clinical development thereof.

The arteriosclerosis is inherently a characteristic lesion such as intima hypertrophy and lipidosis of the blood vessel. According to the recent studies, suppression of foamation of macrophages that play a main role in formation of the arteriosclerosis lesion has been expected to lead to regression of the arteriosclerosis lesion itself. Foam cells derived from macrophages (cholesterol ester is stored in cells as fat droplets) have been observed in the gruel arteriosclerosis lesion, and the foamation of macrophages is deemed to deeply participate in the progression of the lesion. Further, it has been reported that the ACAT activity in the blood vessel wall in the arteriosclerosis lesion site is increased and cholesterol ester is stored in the blood vessel wall (refer to Gillease, J. et al., Exp. Mole. Pathol., 44, 329-339 (1986)).

The inhibition of esterification of cholesterol with an ACAT inhibitor results in formation of free cholesterol in cells, and this free cholesterol is removed with high-density lipoprotein (HDL), transferred to the liver (inversely transferred with HDL), and metabolized. Accordingly, suppression of storage of cholesterol ester in the lesion site is expected. As a result, it is considered to provide a direct anti-arteriosclerotic activity. There is a report that ACAT includes two types, a type present in the small intestine and a type present in the blood vessel wall [Kinunen M. et al., Biochemistry, 27, 7344-7350 (1988)]. However, many of the past researches on the ACAT inhibitor have been conducted using an enzyme of a type present in the small intestine and the liver [Tomoda Elichi et al., J. Antibiotics, 47, 148-153 (1994)].

The present inventors considered that medications which selectively inhibit an ACAT enzyme of a type present in the blood vessel wall can be those for treating arteriosclerosis that give less side effects, and have conducted synthesis and researches of such inhibitors.

The present inventors continued studies for achieving this object, and found in advance that compounds represented by the formula (IV)

-   -   wherein     -   represents an optionally substituted divalent residue such as         benzene, pyridine, cyclohexane or naphthalene or a group,     -   Ar represents an optionally substituted aryl group     -   X represents —NH—, an oxygen atom or a sulfur atom,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom a lower alkyl group, an aryl group         or an optionally substituted silyl lower alkyl group, and     -   n is an integer of from 0 to 15,         or salts or solvates thereof, and compounds represented by the         formula (V)     -   wherein     -   represents an optionally substituted divalent residue such as         benzene, pyridine, cyclohexane or naphthalene, or a group,     -   Ar represents an optionally substituted aryl group,     -   X represents —NH—, an oxygen atom or a sulfur atom,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   l is an integer of from 0 to 15,     -   m is an integer of 2 or 3, and     -   n is integer of from 0 to 3,         or salts or solvates thereof have an excellent ACAT inhibitory         activity, and they applied the same for patents (Japanese Patent         Application Nos. 88,660/1997, 90,146/1997 and 149,892/1997).

Further, as compounds similar to the compounds represented by the formula (I), 3-(benzothiazol-2-ylthio)-N-(phenyl)propanamide is disclosed in J. Chem. Eng. Data, 27, 207 (1982), and 3-(benzoxazol-2-ylthio)-N-(phenyl)propanamide in Fungitsidy, Ed. Melnikov, N. N. Izd. Fan Uzb. SSR: Tashkent, USSR. 82-88 (1980). However, these compounds are not only those in which an amide moiety is a phenyl group, but also these documents are totally devoid of the description that the compounds have an ACAT inhibitory activity.

Thus, the present inventors found that the compounds represented by the formula (IV) or (V) have an organ-selective ACAT inhibitory activity and an intracellular cholesterol transfer inhibitory activity, and that these are useful as an antihyperlipemic agent having an activity of decreasing blood cholesterol and as an agent for preventing and treating arteriosclerosis having a macrophage foamation inhibitory activity.

However, the compounds represented by these formulas (IV) and (V) did not necessarily have a sufficient activity, nor was the organ-selectivity satisfactory.

Under these circumstances, the present inventors have conducted further investigations to develop an ACAT inhibitor having a superior ACAT inhibitory activity, and have consequently found that the compounds represented by the formula (I) are useful ACAT inhibitors which conquer the above-mentioned defects. This finding has led to the completion of the present invention.

DISCLOSURE OF INVENTION

The present invention is to provide compounds represented by the formula (I)

-   -   wherein     -   represents an optionally substituted divalent residue such as         benzene, pyridine, cyclohexane or naphthalene, or a group     -   Met represents a 5- to 8-membered, substituted or unsubstituted         heterocyclic group containing at least one heteroatom selected         from the group consisting of a nitrogen atom, an oxygen atom and         a sulfur atom, such as a monocyclic group, a polycyclic group or         a group of a fused ring.     -   X represents —NH—, an oxygen atom or a sulfur atom,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group, and     -   n is an integer of from 1 to 15,         or salts or solvates thereof.

Further, the present invention is to provide a pharmaceutical composition containing at least one type selected from the compounds represented by the formula (I), and the salts and the solvates thereof in a therapeutically effective amount, and a pharmaceutically acceptable carrier.

Still further, the present invention is to provide an ACAT inhibitor, an intracellular cholesterol transfer inhibitor, a blood cholesterol depressant or a macrophage foamation suppressant containing at least one type selected from the compounds represented by the formula (I), and the salts and the solvates thereof in a therapeutically effective amount, and a pharmaceutically acceptable carrier. That is, the present invention is to provide a medication for treating or preventing diseases such as hyprlipemia, arteriosclerosis, cervical and cerebral arteriosclerosis, cerebrovascular accidents, ischemic heart disease, coronary arteriosclerosis, nephrosclerosis, arteriosclerotic nephrosclerosis, arteriolonephrosclerosis, malignant nephrosclerosis, ischemic intestinal disease, acute occlusion of mesenteric vessel, chronic mesenteric angina, ischemic colitis, aortic aneurysm and arteriosclerosis obliterans (ASO), this medication containing at least one type selected from the compounds represented by the formula (I), and the salts and the solvates thereof, and a pharmaceutically acceptable carrier, as well as a therapeutic method using the same.

BEST MODE FOR CARRYING OUT THE INVENTION

As preferable examples of the compounds represented by the the formula (IA)

-   -   wherein     -   represents an optionally substituted divalent residue such as         benzen or pyridine.     -   Py represents an optionally substituted pyridyl or pyrimidyl         group,     -   X represents —NH—, an oxygen atom or a sulfur atom,     -   Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide         or a sulfone,     -   Z represents a single bond or —NR₅—,     -   R₄ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group,     -   R₅ represents a hydrogen atom, a lower alkyl group, an aryl         group or an optionally substituted silyl lower alkyl group, and     -   n is an integer of from 1 to 15,         or salts or solvates thereof, and a pharmaceutical composition         containing these compounds can be mentioned.

As more preferable examples of the compounds represented by the formula (I) in the present invention, the compounds represented by the formula (II)

-   -   wherein Py represents an optionally substituted pyridyl or         pyrimidyl group, and the other substituents are the same as         described in the above-mentioned the formula (I), and the salts         or the solvates thereof can be mentioned.

As further preferable examples of the compounds represented by the formula (I) in the present invention, the compounds represented by the formula (III)

-   -   wherein     -   W represents ═CH— or ═N—, and     -   R₁, R₂ and R₃ are the same or different, and each represents a         hydrogen atom, a lower alkyl group, a lower alkoxy group, a         halogen atom, a hydroxyl group, a phosphate group, a sulfonamide         group, a lower alkylthio group or an optionally substituted         amino group, or two of R₁, R₂ and R₃ together form an         alkylenedioxide group.

The substituent Het of the compounds represented by the formula (I) in the present invention is a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. This cyclic group may be a monocyclic group, a polycyclic group in which the heterocyclic groups are bound to each other or bound to a carbon ring such as a 6-membered aromatic ring either directly or through a carbon chain, or a group of a fused ring in which the heterocyclic groups are fused to each other or to a carbon ring such as a 6-membered aromatic ring. Among these heterocyclic groups, a 5- to 8-membered heterocyclic group, preferably a 5- or 6-membered heterocyclic group, containing one or two nitrogen atoms is preferable. Preferable examples of the substituent Het include a substituted or unsubstituted pyridyl group, a substituted or unsubstituted pyrimidyl group, a substituted or unsubstituted indolyl group, and a substituted or unsubstituted quinolyl group. A substituted or unsubstituted pyridyl group, and a substituted or unsubstituted pyrimidyl group are further preferable.

These heterocyclic groups may be unsubstituted, but have preferably one or more substituents. The substituent of these heterocyclic groups is not particularly limited unless the ACAT inhibitory activity of the present invention is impaired. Preferable examples thereof include an amino group substituted with a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylcarbonyl group, a halogen atom, an amino group or a lower alkyl group; a substituted or unsubstituted aryl group such as a phenyl group or a naphthyl group; and a substituted or unsubstituted aralkyl group such as a benzyl group or a phenetyl group. Further, two substituents may be bound to form an alkylenedioxy group such as a methylenedioxy group.

As the lower alkyl group, a linear or branched alkyl group having from 1 to 10 carbon atoms, preferably from 1 to 6 carbon atoms is preferable. Especially preferable examples thereof include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl and n-hexyl groups.

As the lower alkyl group in the lower alkoxy group, the lower alkylthio group and the lower alkylcarbonyl group, the above-mentioned linear or branched alkyl group having from 1 to 10 carbon atoms, preferably from 1 to 6 carbon atoms is preferable. Examples thereof include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, methylthio, ethylthio, n-propylthio, iso-propylthio, n-butylthio, iso-butylthio, tert-butylthio, n-pentylthio, n-hexylthio, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, iso-propylcarbonyl, n-butylcarbonyl, iso-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl and n-hexylcarbonyl groups.

Preferable examples of the halogen atom include fluorine, chlorine, bromine and iodine atoms.

As the aryl group, an aryl group having from 6 to 20 carbon atoms, preferably from 6 to 10 carbon atoms is mentioned. This aryl group may be unsubstituted or substituted with the above-mentioned lower alkyl group, lower alkoxy group, lower alkylthio group, lower alkylcarbonyl group, halogen atom, amino group or amino group substituted with the lower alkyl group. Preferable examples of the aryl group include phenyl, naphthyl, 2-methoxyphenyl and 4-methylthiophenyl groups.

The aralkyl group is an aralkyl group having from 7 to 20 carbon atoms, preferably from 7 to 12 carbon atoms. This aralkyl group may be unsubstituted or substituted with the above-mentioned lower alkyl group, lower alkoxy group, lower alkylthio group, lower alkylcarbonyl group, halogen atom, amino group or amino group substituted with the lower alkyl group. Preferable examples of the aralkyl group include benzyl, phenetyl and 4-methylbenzyl groups.

Examples of the substituent in the substituted amino group include the above-mentioned lower alkyl, lower alkylcarbonyl, aryl and aralkyl groups, and the number of the substituent in the amino group may be 1 or 2. Preferable examples of the substituted amino group include methylamino, ethylamino, dimethylamino, diethylamino, acetylamino and benzylamino groups.

The alkylene group of the alkylenedioxy group is a linear or branched alkylene group having from 1 to 10 carbon atoms, preferably from 1 to 5 carbon atoms. Preferable examples thereof include methylenedioxy and ethylenedioxy groups.

As the preferable Het group, a group represented by the formula (VI) is mentioned.

-   -   wherein W, R₁, R₂ and R₃ are as defined above.

Preferable examples of the Het group include

-   -   2-methylthio-3-pyridyl,     -   2-ethylthio-3-pyridyl,     -   2-(iso-propylthio)-3-pyridyl,     -   2-methoxy-3-pyridyl,     -   2-chloro-3-pyridyl,     -   2-methylthio-4-methyl-3-pyridyl,     -   2-ethylthio-4-methyl-3-pyridyl,     -   2-(iso-propylthio)-4-methyl-3-pyridyl,     -   2-methoxy-4-methyl-3-pyridyl,     -   2,6-bis(methylthio)-3-pyridyl,     -   2,6-bis(ethylthio)-3-pyridyl,     -   2,6-bis(iso-propylthio)-3-pyridyl,     -   2-methylthio-6-methoxy-3-pyridyl,     -   2-ethylthio-6-methoxy-3-pyridyl,     -   2-(iso-propylthio)-6-methoxy-3-pyridyl,     -   2-methylthio-6-methyl-3-pyridyl,     -   2-ethylthio-6-methyl-3-pyridyl,     -   2-(iso-propylthio)-6-methyl-3-pyridyl     -   2,6-dimethoxy-3-pyridyl,     -   2-methoxy-6-methyl-3-pyridyl,     -   2-methyl-6-methylthio-3-pyridyl,     -   2-methyl-6-ethylthio-3-pyridyl,     -   2-methyl-6-(iso-propylthio)-3-pyridyl,     -   2-methyl-6-methoxy-3-pyridyl,     -   2,6-dimehtyl-3-pyridyl,     -   2,6-diethyl-3-pyridyl,     -   2,4-bismethylthio-6-methyl-3-pyridyl,     -   2,4-bisethylthio-6-methyl-3-pyridyl,     -   2,4-bis(iso-propylthio)-6-methyl-3-pyridyl,     -   2,4-dimethoxy-6-methyl-3-pyridyl,     -   2,4,6-trimethyl-3-pyridyl,     -   4-ethyl-2,6-dimethyl-3-pyridyl,     -   2,4-dichloro-6-methyl-3-pyridyl,     -   4,6-bis(methylthio)-5-pyrimidyl,     -   4,6-bis(ethylthio)-5-pyrimidyl,     -   4,6-bis(iso-propylthio)-5-pyrimidyl,     -   4,6-dimethoxy-5-pyrimidyl,     -   4,6-dichloro-2-methyl-5-pyrimidyl,     -   4,6-bis(dimethylamino)-5-pyrimidyl,     -   4,6-bismethylthio-2-methyl-5-pyrimidyl,     -   2,4,6-trimethoxy-5-pyrimidyl     -   4-methyl-6-methyltio-3-pyridyl,     -   5-methylthio-2-pyridyl,     -   2,4,6-tris(methylthio)-5-pyrimidyl groups and so on.

The substituent

in the compounds represented by the the formula (I) in the present invention is a divalent group adjacent the azole ring which is formed with two carbon atoms constituting the azole ring. It is preferably an optionally substituted divalent group such as benzene, pyridine, cyclohexane or naphthalene, or a group as follows.

An optionally substituted divalent residue such as benzen or pyridine is preferable. These divalent groups may have a substituent. Examples of the substituent include the above-mentioned lower alkyl group, lower alkoxy group, lower alkylsulfonyl group lower alkylthio group, lower alkylcarbonyl group, halogen atom, amino group, amino group substituted with the lower alkyl group, substituted or unsubstituted aryl group such as the phenyl group or the naphthyl group, and substituted or unsubstituted aralkyl group such as the benzyl group or the phenetyl group. Further, the two substituents may be bound to form an alkylenedioxy group such as a methylenedioxy group.

The substituent X in the compounds represented by the formula (I) in the present invention represents —NH—, an oxygen atom or a sulfur atom, and forms, together with the above-mentioned substituent, an azole ring such as imidazole, oxazole or thiazole.

Further, the substituent Y in the compounds represented by the formula (I) of the present invention represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, and the substituent R₄ of the nitrogen atom represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group. The lower alkyl group or the aryl group as the substituent R₄ is as mentioned above. Examples thereof include methyl, ethyl and phenyl groups. The lower alkyl group of the optionally substituted silyl lower alkyl group as the substituent R₄ may be the above-mentioned group. Examples of the substituent of the silyl lower alkyl group include the above-mentioned lower alkyl, aryl and aralkyl groups. Preferable examples thereof include trimethylsilylmethyl and dimethylphenylsilylmethyl groups.

As the substituent Y, a sulfur atom is preferable.

The substituent Z in the compounds represented by the formula (I) of the present invention represents a single bond or —NR₅—, and the substituent R₅ of the nitrogen atom represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group. Examples of these substituents are the above-mentioned groups.

The number n of recurring units in the compounds represented by the formula (I) in the present invention is an integer of from 1 to 15, preferably an integer of from 1 to 9. As the recurring unit, a methylene group is mentioned in the formula (I). The methylene group may have a substituent or one or more methylene units may be substituted with a heteroatom such as a nitrogen atom, an oxygen atom or a sulfur atom unless the ACAT inhibitory activity of the present invention is impaired.

The substituents X, Y, Z and the recurring unit in the compounds represented by the formula (II) in the present invention are the above-mentioned ones. The substituent Py represents an optionally substituted pyridyl or pyrimidyl group. The substituent of the pyridyl or pyrimidyl group is not particularly limited unless the ACAT inhibitory activity of the present invention is impaired. The group represented by the formula (VI) is preferable.

The substituents X, Y, Z and the recurring unit in the compounds represented by the formula (III) in the present invention are the above-mentioned ones. The substituent W represents a carbon atom or a nitrogen atom, and forms a pyridine or pyrimidine ring. Further, the substituents R₁, R₂ and R₃ are the same or different, and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a hydroxyl group, a phosphate group, a sulfonamide group, a lower alkylthio group or an optionally substituted amino group, or two of R₁, R₂ and R₃ together form an alkylenedioxy group. Of these groups, the lower alkyl group, the lower alkoxy group, the halogen atom, the lower alkylthio group, the optionally substituted amino group and the alkylenedioxy group are the above-mentioned ones. Preferable examples of R₁, R₂ and R₃ include methyl, ethyl, iso-propyl, methoxy, ethoxy and iso-propoxy groups, chlorine, and methylthio, ethylthio, iso-propylthio and dimethylamino groups. The site of the pyridine ring or the pyrimidine ring bound to the adjacent nitrogen atom is not particularly limited either unless the ACAT inhibitory activity of the present invention is impaired.

The salts of the compounds represented by the formula (I), (II) or (III) in the present invention are not particularly limited unless the ACAT inhibitory activity of the present invention is impaired. Acid addition salts or base addition salts can be used as required. Preferable examples of the acid addition salts include inorganic acid salts such as a hydrochloride, a sulfate, a nitrate and a phosphate; and organic acid salts such as a methanesulfonate, a maleate, a fumarate and a citrate.

Further, the solvates of the compounds represented by the formula (I), (II) or (III) in the present invention are products to which solvents used in the production, the purification or the like, such as water, alcohol and the like are added, and are not particularly limited unless they have an adverse effect on the ACAT inhibitory activity. As the solvates, hydrides are preferable.

A process for producing the compounds of the present invention is described below.

Compounds (I) can be produced by various known processes, and the process is not particularly limited. For example, compounds (I) can be produced according to the following reaction steps.

-   1. Process for producing compounds of the formula (I) when the     substituent Z is a single bond:

A carboxylic acid represented by the formula (VII) or its reactive derivative, for example, an acid halide, is reacted with a heterocyclic amine represented by the formula (VIII) according to the following reaction formulae

  wherein R₆ represents a leaving group, and R₇ represents a reactive derivative residue of a hydroxyl group or a carboxylate group, to form an amide derivative represented by the formula (IX). When the resulting compound of the formula (IX) is reacted with an azole derivative represented by the formula (X), a desired compound (I′) in which the substituent Z in the formula (I) is a single bond can be produced.

An ordinary method used in peptide synthesis can be applied to the reaction between compounds (VII) and (VIII). Examples of the leaving group R₆ in the formula (VII) include halogen atoms such as chlorine and bromine atoms. Preferable examples of the reactive derivative residue R₇ include acid anhydride residues with mesylic acid, tosylic acid, acetic acid, pivaloylic acid and the like. This reaction is described more specifically below. The desired compound can be obtained by reacting both of the compounds in a solvent in the presence of a condensation agent. As the condensation agent, for example, 1-(3′-dimethylaminopropyl)-3-ethylcarbodiimide (WSC) and 1,3-dicyclohexylcarbodiimide (DCC) may be used singly, and a combination of 1-hydroxybenzotriazole (HOBt) and N-hydroxysuccinimide (HOSU) is also available. The solvent is not particularly limited. For example, dimethylformamide, methylene chloride, chloroform, tetrahydrofuran and toluene can be used either singly or in combination. The reaction conditions vary depending on a starting material to be used. Generally, the reaction is conducted at from 0 to 100° C., preferably at a temperature close to room temperature, for from 1 to 30 hours, preferably for from 10 to 20 hours. In this manner, the reaction is completed. Further, when a carbonyl halide having a high reactivity is used as compound (VII), for example, compounds (VII) and (VIII) can be reacted in the presence of a base, for example, triethylamine, 4-dimethylaminopyridine or N-methylmorpholine in a usual manner.

With respect to starting compounds (VII) and (VIII), for example, compound (VII) can be produced by a method in which a haloalkyl alcohol is oxidized into a carboxylic acid with a Jones' reagent or the like, and compound (VIII) by a method in which a nitrated heterocyclic compound is subjected to a reduction reaction such as a catalytic reduction or the like to obtain a corresponding amino heterocyclic compound, respectively.

The reaction between compounds (IX) and (X) obtained by the above-mentioned methods can be conducted in a solvent in the presence or absence of a base. As the solvent, the above-mentioned various types can be used. The base includes inorganic bases, for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and alkali metal hydrogencarbonates such as sodium hydrogencarbonate and potassium hydrogencarbonate; and organic bases such as pyridine, triethylamine, N,N-diisopropylethylamine, N-methylmorpholine and N,N-dimethylaniline.

Further, with respect to the desired compound represented by the formula (I′), according to the reaction shown by the following formula

-   -   wherein R₆ represents a leaving group, and R₇ represents a         reactive derivative residue of a hydroxyl group or a carboxylate         group, an azole derivative represented by the formula (X) is         reacted with a free carboxylic acid or an inactive substance of         a carboxylic acid as the compound represented by the         formula (VII) to obtain a carboxylic acid derivative represented         by the formula (XI). When the resulting compound represented by         the formula (XI) or its reactive derivative, for example, an         acid halide, is reacted with a heterocyclic amine derivative         represented by the formula (VIII), the desired compound (I′) in         which the substituent Z in the formula (I) is a single bond can         be produced.

The reaction between compounds (X) and (VII) can be conducted according to the second step of the above-mentioned reaction formula. The reaction in which potassium hydroxide is used as a base and ethanol as a solvent respectively is especially preferable. The reaction between the resulting compounds (XI) and (VIII) can be conducted according to the first step of the above-mentioned reaction formula.

-   2. Process for producing compounds of the formula (I) when the     substituent Z is —NH—:

The compound represented by the formula (I) in which Z is —NH— can be produced by various processes. It is preferable to produce the same by the process shown by the following reaction formula.

-   -   wherein R₈ represents a leaving group.

The isocyanate derivative represented by the formula (XII) is reacted with the heterocyclic amine represented by the formula (VIII) to obtain an urea derivative represented by the formula (XIII). The resulting urea derivative is reacted with compound (X) to form desired compound (I″) in which the substituent Z in the formula (I) is —NH—.

With respect to the reaction between compounds (XII) and (VIII) in the first step of this reaction formula, compound (XII) is reacted with compound (VIII) in an amount of from 1 to 2 equivalents in a solvent to obtain compound (XIII). At this time, the solvent is not particularly limited. Preferable examples thereof include methylene chloride, chloroform, ether, tetrahydrofuran, toluene, xylene and dimethylformamide. The reaction proceeds in a boiling point of a solvent used from 0° C. for a reaction time of from 1 to 24 hours.

The isocyanate derivative represented by the formula (XII) is a known compound, and it can be produced by, for example, a method in which the above-mentioned carboxylic acid as compound (VII) is reacted with diphenylphospholyl azide in the presence of a base (method of Shioiri et al.), a method via an acid azide by reacting the acid halide of compound (VII) with sodium azide.

The reaction between compounds (XIII) and (X) can be conducted according to the second step of the above-mentioned reaction formula.

Further, when the substituent Z in the formula (I) is —NR₅— (wherein R₅ represents the above-mentioned groups except a hydrogen atom), the compound can be produced by replacing a nitrogen atom with the substituent R₅ at an appropriate stage.

The intermediate and the desired compound obtained in each of the above-mentioned reactions can be isolated and purified by a purification method which is ordinarily used in the synthetic organic chemistry, such as filtration, extraction, washing, drying, concentration, recrystallization and various chromatographies. Further, each intermediate is subjected to the subsequent step without any purification unless any trouble is caused, which is well known to those skilled in the art.

The resulting compounds (I) can be formed into salts of the present invention in a usual manner.

Further, compounds (I) can be formed into solvates with solvents such as a reaction solvent, a recrystallization solvent and the like, especially hydrides in a usual manner, which is well known to those skilled in the art.

The compounds represented by the formula (I), (II) or (III), which are obtained by the process of the present invention are shown in Tables 1 to 63 below.

TABLE 1 Compound No.

X Y Z n Het  1

O S * 1 2-methylthio-3-pyridyl  2 ″ O S * 2 2-methylthio-3-pyridyl  3 ″ O S * 3 2-methylthio-3-pyridyl  4 ″ O S * 4 2-methylthio-3-pyridyl  5 ″ O S * 5 2-methylthio-3-pyridyl  6 ″ O S * 6 2-methylthio-3-pyridyl  7 ″ O S * 7 2-methylthio-3-pyridyl  8 ″ O S * 8 2-methylthio-3-pyridyl  9 ″ O S * 9 2-methylthio-3-pyridyl 10 ″ O S * 14 2-methylthio-3-pyridyl 11 ″ S S * 1 2-methylthio-3-pyridyl 12 ″ S S * 2 2-methylthio-3-pyridyl 13 ″ S S * 3 2-methylthio-3-pyridyl 14 ″ S S * 4 2-methylthio-3-pyridyl 15 ″ S S * 5 2-methylthio-3-pyridyl 16 ″ S S * 6 2-methylthio-3-pyridyl 17 ″ S S * 7 2-methylthio-3-pyridyl 18 ″ S S * 8 2-methylthio-3-pyridyl 19 ″ S S * 9 2-methylthio-3-pyridyl 20 ″ S S * 14 2-methylthio-3-pyridyl *: Single Bond  

TABLE 2 Compound No.

X Y Z n Het 21

NH S * 1 2-methylthio-3- pyridyl 22 ″ NH S * 2 2-methylthio-3- pyridyl 23 ″ NH S * 3 2-methylthio-3- pyridyl 24 ″ NH S * 4 2-methylthio-3- pyridyl 25 ″ NH S * 5 2-methylthio-3- pyridyl 26 ″ NH S * 6 2-methylthio-3- pyridyl 27 ″ NH S * 7 2-methylthio-3- pyridyl 28 ″ NH S * 8 2-methylthio-3- pyridyl 29 ″ NH S * 9 2-methylthio-3- pyridyl 30 ″ NH S * 14 2-methylthio-3- pyridyl 31 ″ O S * 1 2-ethylthio-3- pyridyl 32 ″ O S * 2 2-ethylthio-3- pyridyl 33 ″ O S * 3 2-ethylthio-3- pyridyl 34 ″ O S * 4 2-ethylthio-3- pyridyl 35 ″ O S * 5 2-ethylthio-3- pyridyl 36 ″ O S * 6 2-ethylthio-3- pyridyl 37 ″ O S * 7 2-ethylthio-3- pyridyl 38 ″ O S * 8 2-ethylthio-3- pyridyl 39 ″ O S * 9 2-ethylthio-3- pyridyl 40 ″ O S * 14 2-ethylthio-3- pyridyl *: Single Bond  

TABLE 3 Compound No.

X Y Z n Het 41

S S * 1 2-ethylthio-3- pyridyl 42 ″ S S * 2 2-ethylthio-3- pyridyl 43 ″ S S * 3 2-ethylthio-3- pyridyl 44 ″ S S * 4 2-ethylthio-3- pyridyl 45 ″ S S * 5 2-ethylthio-3- pyridyl 46 ″ S S * 6 2-ethylthio-3- pyridyl 47 ″ S S * 7 2-ethylthio-3- pyridyl 48 ″ S S * 8 2-ethylthio-3- pyridyl 49 ″ S S * 9 2-ethylthio-3- pyridyl 50 ″ S S * 14 2-ethylthio-3- pyridyl 51 ″ NH S * 1 2-ethylthio-3- pyridyl 52 ″ NH S * 2 2-ethylthio-3- pyridyl 53 ″ NH S * 3 2-ethylthio-3- pyridyl 54 ″ NH S * 4 2-ethylthio-3- pyridyl 55 ″ NH S * 5 2-ethylthio-3- pyridyl 56 ″ NH S * 6 2-ethylthio-3- pyridyl 57 ″ NH S * 7 2-ethylthio-3- pyridyl 58 ″ NH S * 8 2-ethylthio-3- pyridyl 59 ″ NH S * 9 2-ethylthio-3- pyridyl 60 ″ NH S * 14 2-ethylthio-3- pyridyl *: Single Bond  

TABLE 4 Compound No.

X Y Z n Het 61

O S * 1 2-(iso-propylthio)-3- pyridyl 62 ″ O S * 2 2-(iso-propylthio)-3- pyridyl 63 ″ O S * 3 2-(iso-propylthio)-3- pyridyl 64 ″ O S * 4 2-(iso-propylthio)-3- pyridyl 65 ″ O S * 5 2-(iso-propylthio)-3- pyridyl 66 ″ O S * 6 2-(iso-propylthio)-3- pyridyl 67 ″ O S * 7 2-(iso-propylthio)-3- pyridyl 68 ″ O S * 8 2-(iso-propylthio)-3- pyridyl 69 ″ O S * 9 2-(iso-propylthio)-3- pyridyl 70 ″ O S * 14 2-(iso-propylthio)-3- pyridyl 71 ″ S S * 1 2-(iso-propylthio)-3- pyridyl 72 ″ S S * 2 2-(iso-propylthio)-3- pyridyl 73 ″ S S * 3 2-(iso-propylthio)-3- pyridyl 74 ″ S S * 4 2-(iso-propylthio)-3- pyridyl 75 ″ S S * 5 2-(iso-propylthio)-3- pyridyl 76 ″ S S * 6 2-(iso-propylthio)-3- pyridyl 77 ″ S S * 7 2-(iso-propylthio)-3- pyridyl 78 ″ S S * 8 2-(iso-propylthio)-3- pyridyl 79 ″ S S * 9 2-(iso-propylthio)-3- pyridyl 80 ″ S S * 14 2-(iso-propylthio)-3- pyridyl *: Single Bond  

TABLE 5 Compound No.

X Y Z n Het  81

NH S * 1 2-(iso-propylthio)-3- pyridyl  82 ″ NH S * 2 2-(iso-propylthio)-3- pyridyl  83 ″ NH S * 3 2-(iso-propylthio)-3- pyridyl  84 ″ NH S * 4 2-(iso-propylthio)-3- pyridyl  85 ″ NH S * 5 2-(iso-propylthio)-3- pyridyl  86 ″ NH S * 6 2-(iso-propylthio)-3- pyridyl  87 ″ NH S * 7 2-(iso-propylthio)-3- pyridyl  88 ″ NH S * 8 2-(iso-propylthio)-3- pyridyl  89 ″ NH S * 9 2-(iso-propylthio)-3- pyridyl  90 ″ NH S * 14 2-(iso-propylthio)-3- pyridyl  91 ″ O S * 1 2-methoxy-3-pyridyl  92 ″ O S * 2 2-methoxy-3-pyridyl  93 ″ O S * 3 2-methoxy-3-pyridyl  94 ″ O S * 4 2-methoxy-3-pyridyl  95 ″ O S * 5 2-methoxy-3-pyridyl  96 ″ O S * 6 2-methoxy-3-pyridyl  97 ″ O S * 7 2-methoxy-3-pyridyl  98 ″ O S * 8 2-methoxy-3-pyridyl  99 ″ O S * 9 2-methoxy-3-pyridyl 100 ″ O S * 14 2-methoxy-3-pyridyl *: Single Bond  

TABLE 6 Compound No.

X Y Z n Het 101

S S * 1 2-methoxy-3-pyridyl 102 ″ S S * 2 2-methoxy-3-pyridyl 103 ″ S S * 3 2-methoxy-3-pyridyl 104 ″ S S * 4 2-methoxy-3-pyridyl 105 ″ S S * 5 2-methoxy-3-pyridyl 106 ″ S S * 6 2-methoxy-3-pyridyl 107 ″ S S * 7 2-methoxy-3-pyridyl 108 ″ S S * 8 2-methoxy-3-pyridyl 109 ″ S S * 9 2-methoxy-3-pyridyl 110 ″ S S * 14 2-methoxy-3-pyridyl 111 ″ NH S * 1 2-methoxy-3-pyridyl 112 ″ NH S * 2 2-methoxy-3-pyridyl 113 ″ NH S * 3 2-methoxy-3-pyridyl 114 ″ NH S * 4 2-methoxy-3-pyridyl 115 ″ NH S * 5 2-methoxy-3-pyridyl 116 ″ NH S * 6 2-methoxy-3-pyridyl 117 ″ NH S * 7 2-methoxy-3-pyridyl 118 ″ NH S * 8 2-methoxy-3-pyridyl 119 ″ NH S * 9 2-methoxy-3-pyridyl 120 ″ NH S * 14 2-methoxy-3-pyridyl *: Single Bond  

TABLE 7 Compound No.

X Y Z n Het 121

O S * 1 2-chloro-3-pyridyl 122 ″ O S * 2 2-chloro-3-pyridyl 123 ″ O S * 3 2-chloro-3-pyridyl 124 ″ O S * 4 2-chloro-3-pyridyl 125 ″ O S * 5 2-chloro-3-pyridyl 126 ″ O S * 6 2-chloro-3-pyridyl 127 ″ O S * 7 2-chloro-3-pyridyl 128 ″ O S * 8 2-chloro-3-pyridyl 129 ″ O S * 9 2-chloro-3-pyridyl 130 ″ O S * 14 2-chloro-3-pyridyl 131 ″ S S * 1 2-chloro-3-pyridyl 132 ″ S S * 2 2-chloro-3-pyridyl 133 ″ S S * 3 2-chloro-3-pyridyl 134 ″ S S * 4 2-chloro-3-pyridyl 135 ″ S S * 5 2-chloro-3-pyridyl 136 ″ S S * 6 2-chloro-3-pyridyl 137 ″ S S * 7 2-chloro-3-pyridyl 138 ″ S S * 8 2-chloro-3-pyridyl 139 ″ S S * 9 2-chloro-3-pyridyl 140 ″ S S * 14 2-chloro-3-pyridyl *: Single Bond  

TABLE 8 Compound No.

X Y Z n Het 141

NH S * 1 2-chloro-3-pyridyl 142 ″ NH S * 2 2-chloro-3-pyridyl 143 ″ NH S * 3 2-chloro-3-pyridyl 144 ″ NH S * 4 2-chloro-3-pyridyl 145 ″ NH S * 5 2-chloro-3-pyridyl 146 ″ NH S * 6 2-chloro-3-pyridyl 147 ″ NH S * 7 2-chloro-3-pyridyl 148 ″ NH S * 8 2-chloro-3-pyridyl 149 ″ NH S * 9 2-chloro-3-pyridyl 150 ″ NH S * 14 2-chloro-3-pyridyl 151 ″ O S * 1 2-methylthio-4- methyl-3-pyridyl 152 ″ O S * 2 2-methylthio-4- methyl-3-pyridyl 153 ″ O S * 3 2-methylthio-4- methyl-3-pyridyl 154 ″ O S * 4 2-methylthio-4- methyl-3-pyridyl 155 ″ O S * 5 2-methylthio-4- methyl-3-pyridyl 156 ″ O S * 6 2-methylthio-4- methyl-3-pyridyl 157 ″ O S * 7 2-methylthio-4- methyl-3-pyridyl 158 ″ O S * 8 2-methylthio-4- methyl-3-pyridyl 159 ″ O S * 9 2-methylthio-4- methyl-3-pyridyl 160 ″ O S * 14 2-methylthio-4- methyl-3-pyridyl *: Single Bond  

TABLE 9 Compound No.

X Y Z n Het 161

S S * 1 2-methylthio-4- methyl-3-pyridyl 162 ″ S S * 2 2-methylthio-4- methyl-3-pyridyl 163 ″ S S * 3 2-methylthio-4- methyl-3-pyridyl 164 ″ S S * 4 2-methylthio-4- methyl-3-pyridyl 165 ″ S S * 5 2-methylthio-4- methyl-3-pyridyl 166 ″ S S * 6 2-methylthio-4- methyl-3-pyridyl 167 ″ S S * 7 2-methylthio-4- methyl-3-pyridyl 168 ″ S S * 8 2-methylthio-4- methyl-3-pyridyl 169 ″ S S * 9 2-methylthio-4- methyl-3-pyridyl 170 ″ S S * 14 2-methylthio-4- methyl-3-pyridyl 171 ″ NH S * 1 2-methylthio-4- methyl-3-pyridyl 172 ″ NH S * 2 2-methylthio-4- methyl-3-pyridyl 173 ″ NH S * 3 2-methylthio-4- methyl-3-pyridyl 174 ″ NH S * 4 2-methylthio-4- methyl-3-pyridyl 175 ″ NH S * 5 2-methylthio-4- methyl-3-pyridyl 176 ″ NH S * 6 2-methylthio-4- methyl-3-pyridyl 177 ″ NH S * 7 2-methylthio-4- methyl-3-pyridyl 178 ″ NH S * 8 2-methylthio-4- methyl-3-pyridyl 179 ″ NH S * 9 2-methylthio-4- methyl-3-pyridyl 180 ″ NH S * 14 2-methylthio-4- methyl-3-pyridyl *: Single Bond  

TABLE 10 Compound No.

X Y Z n Het 181

O S * 1 2-ethylthio-4-methyl- 3-pyridyl 182 ″ O S * 2 2-ethylthio-4-methyl- 3-pyridyl 183 ″ O S * 3 2-ethylthio-4-methyl- 3-pyridyl 184 ″ O S * 4 2-ethylthio-4-methyl- 3-pyridyl 185 ″ O S * 5 2-ethylthio-4-methyl- 3-pyridyl 186 ″ O S * 6 2-ethylthio-4-methyl- 3-pyridyl 187 ″ O S * 7 2-ethylthio-4-methyl- 3-pyridyl 188 ″ O S * 8 2-ethylthio-4-methyl- 3-pyridyl 189 ″ O S * 9 2-ethylthio-4-methyl- 3-pyridyl 190 ″ O S * 14 2-ethylthio-4-methyl- 3-pyridyl 191 ″ S S * 1 2-ethylthio-4-methyl- 3-pyridyl 192 ″ S S * 2 2-ethylthio-4-methyl- 3-pyridyl 193 ″ S S * 3 2-ethylthio-4-methyl- 3-pyridyl 194 ″ S S * 4 2-ethylthio-4-methyl- 3-pyridyl 195 ″ S S * 5 2-ethylthio-4-methyl- 3-pyridyl 196 ″ S S * 6 2-ethylthio-4-methyl- 3-pyridyl 197 ″ S S * 7 2-ethylthio-4-methyl- 3-pyridyl 198 ″ S S * 8 2-ethylthio-4-methyl- 3-pyridyl 199 ″ S S * 9 2-ethylthio-4-methyl- 3-pyridyl 200 ″ S S * 14 2-ethylthio-4-methyl- 3-pyridyl *: Single Bond  

TABLE 11 Compound No.

X Y Z n Het 201

NH S * 1 2-ethylthio-4- methyl-3-pyridyl 202 ″ NH S * 2 2-ethylthio-4- methyl-3-pyridyl 203 ″ NH S * 3 2-ethylthio-4- methyl-3-pyridyl 204 ″ NH S * 4 2-ethylthio-4- methyl-3-pyridyl 205 ″ NH S * 5 2-ethylthio-4- methyl-3-pyridyl 206 ″ NH S * 6 2-ethylthio-4- methyl-3-pyridyl 207 ″ NH S * 7 2-ethylthio-4- methyl-3-pyridyl 208 ″ NH S * 8 2-ethylthio-4- methyl-3-pyridyl 209 ″ NH S * 9 2-ethylthio-4- methyl-3-pyridyl 210 ″ NH S * 14 2-ethylthio-4- methyl-3-pyridyl 211 ″ O S * 1 2-(iso-propylthio)-4- methyl-3-pyridyl 212 ″ O S * 2 2-(iso-propylthio)-4- methyl-3-pyridyl 213 ″ O S * 3 2-(iso-propylthio)-4- methyl-3-pyridyl 214 ″ O S * 4 2-(iso-propylthio)-4- methyl-3-pyridyl 215 ″ O S * 5 2-(iso-propylthio)-4- methyl-3-pyridyl 216 ″ O S * 6 2-(iso-propylthio)-4- methyl-3-pyridyl 217 ″ O S * 7 2-(iso-propylthio)-4- methyl-3-pyridyl 218 ″ O S * 8 2-(iso-propylthio)-4- methyl-3-pyridyl 219 ″ O S * 9 2-(iso-propylthio)-4- methyl-3-pyridyl 220 ″ O S * 14 2-(iso-propylthio)-4- methyl-3-pyridyl *: Single Bond  

TABLE 12 Compound No.

X Y Z n Het 221

S S * 1 2-(iso-propylthio)-4- methyl-3-pyridyl 222 ″ S S * 2 2-(iso-propylthio)-4- methyl-3-pyridyl 223 ″ S S * 3 2-(iso-propylthio)-4- methyl-3-pyridyl 224 ″ S S * 4 2-(iso-propylthio)-4- methyl-3-pyridyl 225 ″ S S * 5 2-(iso-propylthio)-4- methyl-3-pyridyl 226 ″ S S * 6 2-(iso-propylthio)-4- methyl-3-pyridyl 227 ″ S S * 7 2-(iso-propylthio)-4- methyl-3-pyridyl 228 ″ S S * 8 2-(iso-propylthio)-4- methyl-3-pyridyl 229 ″ S S * 9 2-(iso-propylthio)-4- methyl-3-pyridyl 230 ″ S S * 14 2-(iso-propylthio)-4- methyl-3-pyridyl 231 ″ NH S * 1 2-(iso-propylthio)-4- methyl-3-pyridyl 232 ″ NH S * 2 2-(iso-propylthio)-4- methyl-3-pyridyl 233 ″ NH S * 3 2-(iso-propylthio)-4- methyl-3-pyridyl 234 ″ NH S * 4 2-(iso-propylthio)-4- methyl-3-pyridyl 235 ″ NH S * 5 2-(iso-propylthio)-4- methyl-3-pyridyl 236 ″ NH S * 6 2-(iso-propylthio)-4- methyl-3-pyridyl 237 ″ NH S * 7 2-(iso-propylthio)-4- methyl-3-pyridyl 238 ″ NH S * 8 2-(iso-propylthio)-4- methyl-3-pyridyl 239 ″ NH S * 9 2-(iso-propylthio)-4- methyl-3-pyridyl 240 ″ NH S * 14 2-(iso-propylthio)-4- methyl-3-pyridyl *: Single Bond  

TABLE 13 Compound No.

X Y Z n Het 241

O S * 1 2-methoxy-4-methyl- 3-pyridyl 242 ″ O S * 2 2-methoxy-4-methyl- 3-pyridyl 243 ″ O S * 3 2-methoxy-4-methyl- 3-pyridyl 244 ″ O S * 4 2-methoxy-4-methyl- 3-pyridyl 245 ″ O S * 5 2-methoxy-4-methyl- 3-pyridyl 246 ″ O S * 6 2-methoxy-4-methyl- 3-pyridyl 247 ″ O S * 7 2-methoxy-4-methyl- 3-pyridyl 248 ″ O S * 8 2-methoxy-4-methyl- 3-pyridyl 249 ″ O S * 9 2-methoxy-4-methyl- 3-pyridyl 250 ″ O S * 14 2-methoxy-4-methyl- 3-pyridyl 251 ″ S S * 1 2-methoxy-4-methyl- 3-pyridyl 252 ″ S S * 2 2-methoxy-4-methyl- 3-pyridyl 253 ″ S S * 3 2-methoxy-4-methyl- 3-pyridyl 254 ″ S S * 4 2-methoxy-4-methyl- 3-pyridyl 255 ″ S S * 5 2-methoxy-4-methyl- 3-pyridyl 256 ″ S S * 6 2-methoxy-4-methyl- 3-pyridyl 257 ″ S S * 7 2-methoxy-4-methyl- 3-pyridyl 258 ″ S S * 8 2-methoxy-4-methyl- 3-pyridyl 259 ″ S S * 9 2-methoxy-4-methyl- 3-pyridyl 260 ″ S S * 14 2-methoxy-4-methyl- 3-pyridyl *: Single Bond  

TABLE 14 Compound No.

X Y Z n Het 261

NH S * 1 2-methoxy-4- methyl-3-pyridyl 262 ″ NH S * 2 2-methoxy-4- methyl-3-pyridyl 263 ″ NH S * 3 2-methoxy-4- methyl-3-pyridyl 264 ″ NH S * 4 2-methoxy-4- methyl-3-pyridyl 265 ″ NH S * 5 2-methoxy-4- methyl-3-pyridyl 266 ″ NH S * 6 2-methoxy-4- methyl-3-pyridyl 267 ″ NH S * 7 2-methoxy-4- methyl-3-pyridyl 268 ″ NH S * 8 2-methoxy-4- methyl-3-pyridyl 269 ″ NH S * 9 2-methoxy-4- methyl-3-pyridyl 270 ″ NH S * 14 2-methoxy-4- methyl-3-pyridyl 271 ″ O S * 1 2,6-bismethylthio-3- pyridyl 272 ″ O S * 2 2,6-bismethylthio-3- pyridyl 273 ″ O S * 3 2,6-bismethylthio-3- pyridyl 274 ″ O S * 4 2,6-bismethylthio-3- pyridyl 275 ″ O S * 5 2,6-bismethylthio-3- pyridyl 276 ″ O S * 6 2,6-bismethylthio-3- pyridyl 277 ″ O S * 7 2,6-bismethylthio-3- pyridyl 278 ″ O S * 8 2,6-bismethylthio-3- pyridyl 279 ″ O S * 9 2,6-bismethylthio-3- pyridyl 280 ″ O S * 14 2,6-bismethylthio-3- pyridyl *: Single Bond  

TABLE 15 Compound No.

X Y Z n Het 281

S S * 1 2,6-bismethylthio-3- pyridyl 282 ″ S S * 2 2,6-bismethylthio-3- pyridyl 283 ″ S S * 3 2,6-bismethylthio-3- pyridyl 284 ″ S S * 4 2,6-bismethylthio-3- pyridyl 285 ″ S S * 5 2,6-bismethylthio-3- pyridyl 286 ″ S S * 6 2,6-bismethylthio-3- pyridyl 287 ″ S S * 7 2,6-bismethylthio-3- pyridyl 288 ″ S S * 8 2,6-bismethylthio-3- pyridyl 289 ″ S S * 9 2,6-bismethylthio-3- pyridyl 290 ″ S S * 14 2,6-bismethylthio-3- pyridyl 291 ″ NH S * 1 2,6-bismethylthio-3- pyridyl 292 ″ NH S * 2 2,6-bismethylthio-3- pyridyl 293 ″ NH S * 3 2,6-bismethylthio-3- pyridyl 294 ″ NH S * 4 2,6-bismethylthio-3- pyridyl 295 ″ NH S * 5 2,6-bismethylthio-3- pyridyl 296 ″ NH S * 6 2,6-bismethylthio-3- pyridyl 297 ″ NH S * 7 2,6-bismethylthio-3- pyridyl 298 ″ NH S * 8 2,6-bismethylthio-3- pyridyl 299 ″ NH S * 9 2,6-bismethylthio-3- pyridyl 300 ″ NH S * 14 2,6-bismethylthio-3- pyridyl *: Single Bond  

TABLE 16 Compound No.

X Y Z n Het 301

O S * 1 2,6-bisethylthio-3- pyridyl 302 ″ O S * 2 2,6-bisethylthio-3- pyridyl 303 ″ O S * 3 2,6-bisethylthio-3- pyridyl 304 ″ O S * 4 2,6-bisethylthio-3- pyridyl 305 ″ O S * 5 2,6-bisethylthio-3- pyridyl 306 ″ O S * 6 2,6-bisethylthio-3- pyridyl 307 ″ O S * 7 2,6-bisethylthio-3- pyridyl 308 ″ O S * 8 2,6-bisethylthio-3- pyridyl 309 ″ O S * 9 2,6-bisethylthio-3- pyridyl 310 ″ O S * 14 2,6-bisethylthio-3- pyridyl 311 ″ S S * 1 2,6-bisethylthio-3- pyridyl 312 ″ S S * 2 2,6-bisethylthio-3- pyridyl 313 ″ S S * 3 2,6-bisethylthio-3- pyridyl 314 ″ S S * 4 2,6-bisethylthio-3- pyridyl 315 ″ S S * 5 2,6-bisethylthio-3- pyridyl 316 ″ S S * 6 2,6-bisethylthio-3- pyridyl 317 ″ S S * 7 2,6-bisethylthio-3- pyridyl 318 ″ S S * 8 2,6-bisethylthio-3- pyridyl 319 ″ S S * 9 2,6-bisethylthio-3- pyridyl 320 ″ S S * 14 2,6-bisethylthio-3- pyridyl *: Single Bond  

TABLE 17 Compound No.

X Y Z n Het 321

NH S * 1 2,6-bisethylthio-3- pyridyl 322 ″ NH S * 2 2,6-bisethylthio-3- pyridyl 323 ″ NH S * 3 2,6-bisethylthio-3- pyridyl 324 ″ NH S * 4 2,6-bisethylthio-3- pyridyl 325 ″ NH S * 5 2,6-bisethylthio-3- pyridyl 326 ″ NH S * 6 2,6-bisethylthio-3- pyridyl 327 ″ NH S * 7 2,6-bisethylthio-3- pyridyl 328 ″ NH S * 8 2,6-bisethylthio-3- pyridyl 329 ″ NH S * 9 2,6-bisethylthio-3- pyridyl 330 ″ NH S * 14 2,6-bisethylthio-3- pyridyl 331 ″ O S * 1 2,6-bis(iso-propyl- thio)-3-pyridyl 332 ″ O S * 2 2,6-bis(iso-propyl- thio)-3-pyridyl 333 ″ O S * 3 2,6-bis(iso-propyl- thio)-3-pyridyl 334 ″ O S * 4 2,6-bis(iso-propyl- thio)-3-pyridyl 335 ″ O S * 5 2,6-bis(iso-propyl- thio)-3-pyridyl 336 ″ O S * 6 2,6-bis(iso-propyl- thio)-3-pyridyl 337 ″ O S * 7 2,6-bis(iso-propyl- thio)-3-pyridyl 338 ″ O S * 8 2,6-bis(iso-propyl- thio)-3-pyridyl 339 ″ O S * 9 2,6-bis(iso-propyl- thio)-3-pyridyl 340 ″ O S * 14 2,6-bis(iso-propyl- thio)-3-pyridyl *: Single Bond  

TABLE 18 Compound No.

X Y Z n Het 341

S S * 1 2,6-bis(iso-propyl- thio)-3-pyridyl 342 ″ S S * 2 2,6-bis(iso-propyl- thio)-3-pyridyl 343 ″ S S * 3 2,6-bis(iso-propyl- thio)-3-pyridyl 344 ″ S S * 4 2,6-bis(iso-propyl- thio)-3-pyridyl 345 ″ S S * 5 2,6-bis(iso-propyl- thio)-3-pyridyl 346 ″ S S * 6 2,6-bis(iso-propyl- thio)-3-pyridyl 347 ″ S S * 7 2,6-bis(iso-propyl- thio)-3-pyridyl 348 ″ S S * 8 2,6-bis(iso-propyl- thio)-3-pyridyl 349 ″ S S * 9 2,6-bis(iso-propyl- thio)-3-pyridyl 350 ″ S S * 14 2,6-bis(iso-propyl- thio)-3-pyridyl 351 ″ NH S * 1 2,6-bis(iso-propyl- thio)-3-pyridyl 352 ″ NH S * 2 2,6-bis(iso-propyl- thio)-3-pyridyl 353 ″ NH S * 3 2,6-bis(iso-propyl- thio)-3-pyridyl 354 ″ NH S * 4 2,6-bis(iso-propyl- thio)-3-pyridyl 355 ″ NH S * 5 2,6-bis(iso-propyl- thio)-3-pyridyl 356 ″ NH S * 6 2,6-bis(iso-propyl- thio)-3-pyridyl 357 ″ NH S * 7 2,6-bis(iso-propyl- thio)-3-pyridyl 358 ″ NH S * 8 2,6-bis(iso-propyl- thio)-3-pyridyl 359 ″ NH S * 9 2,6-bis(iso-propyl- thio)-3-pyridyl 360 ″ NH S * 14 2,6-bis(iso-propyl- thio)-3-pyridyl *: Single Bond  

TABLE 19 Compound No.

X Y Z n Het 361

O S * 1 2-methylthio-6- methoxy-3-pyridyl 362 ″ O S * 2 2-methylthio-6- methoxy-3-pyridyl 363 ″ O S * 3 2-methylthio-6- methoxy-3-pyridyl 364 ″ O S * 4 2-methylthio-6- methoxy-3-pyridyl 365 ″ O S * 5 2-methylthio-6- methoxy-3-pyridyl 366 ″ O S * 6 2-methylthio-6- methoxy-3-pyridyl 367 ″ O S * 7 2-methylthio-6- methoxy-3-pyridyl 368 ″ O S * 8 2-methylthio-6- methoxy-3-pyridyl 369 ″ O S * 9 2-methylthio-6- methoxy-3-pyridyl 370 ″ O S * 14 2-methylthio-6- methoxy-3-pyridyl 371 ″ S S * 1 2-methylthio-6- methoxy-3-pyridyl 372 ″ S S * 2 2-methylthio-6- methoxy-3-pyridyl 373 ″ S S * 3 2-methylthio-6- methoxy-3-pyridyl 374 ″ S S * 4 2-methylthio-6- methoxy-3-pyridyl 375 ″ S S * 5 2-methylthio-6- methoxy-3-pyridyl 376 ″ S S * 6 2-methylthio-6- methoxy-3-pyridyl 377 ″ S S * 7 2-methylthio-6- methoxy-3-pyridyl 378 ″ S S * 8 2-methylthio-6- methoxy-3-pyridyl 379 ″ S S * 9 2-methylthio-6- methoxy-3-pyridyl 380 ″ S S * 14 2-methylthio-6- methoxy-3-pyridyl *: Single Bond  

TABLE 20 Compound No.

X Y Z n Het 381

NH S * 1 2-methylthio-6- methoxy-3-pyridyl 382 ″ NH S * 2 2-methylthio-6- methoxy-3-pyridyl 383 ″ NH S * 3 2-methylthio-6- methoxy-3-pyridyl 384 ″ NH S * 4 2-methylthio-6- methoxy-3-pyridyl 385 ″ NH S * 5 2-methylthio-6- methoxy-3-pyridyl 386 ″ NH S * 6 2-methylthio-6- methoxy-3-pyridyl 387 ″ NH S * 7 2-methylthio-6- methoxy-3-pyridyl 388 ″ NH S * 8 2-methylthio-6- methoxy-3-pyridyl 389 ″ NH S * 9 2-methylthio-6- methoxy-3-pyridyl 390 ″ NH S * 14 2-methylthio-6- methoxy-3-pyridyl 391 ″ O S * 1 2-ethylthio-6- methoxy-3-pyridyl 392 ″ O S * 2 2-ethylthio-6- methoxy-3-pyridyl 393 ″ O S * 3 2-ethylthio-6- methoxy-3-pyridyl 394 ″ O S * 4 2-ethylthio-6- methoxy-3-pyridyl 395 ″ O S * 5 2-ethylthio-6- methoxy-3-pyridyl 396 ″ O S * 6 2-ethylthio-6- methoxy-3-pyridyl 397 ″ O S * 7 2-ethylthio-6- methoxy-3-pyridyl 398 ″ O S * 8 2-ethylthio-6- methoxy-3-pyridyl 399 ″ O S * 9 2-ethylthio-6- methoxy-3-pyridyl 400 ″ O S * 14 2-ethylthio-6- methoxy-3-pyridyl *: Single Bond  

TABLE 21 Compound No.

X Y Z n Het 401

S S * 1 2-ethylthio-6- methoxy-3-pyridyl 402 ″ S S * 2 2-ethylthio-6- methoxy-3-pyridyl 403 ″ S S * 3 2-ethylthio-6- methoxy-3-pyridyl 404 ″ S S * 4 2-ethylthio-6- methoxy-3-pyridyl 405 ″ S S * 5 2-ethylthio-6- methoxy-3-pyridyl 406 ″ S S * 6 2-ethylthio-6- methoxy-3-pyridyl 407 ″ S S * 7 2-ethylthio-6- methoxy-3-pyridyl 408 ″ S S * 8 2-ethylthio-6- methoxy-3-pyridyl 409 ″ S S * 9 2-ethylthio-6- methoxy-3-pyridyl 410 ″ S S * 14 2-ethylthio-6- methoxy-3-pyridyl 411 ″ NH S * 1 2-ethylthio-6- methoxy-3-pyridyl 412 ″ NH S * 2 2-ethylthio-6- methoxy-3-pyridyl 413 ″ NH S * 3 2-ethylthio-6- methoxy-3-pyridyl 414 ″ NH S * 4 2-ethylthio-6- methoxy-3-pyridyl 415 ″ NH S * 5 2-ethylthio-6- methoxy-3-pyridyl 416 ″ NH S * 6 2-ethylthio-6- methoxy-3-pyridyl 417 ″ NH S * 7 2-ethylthio-6- methoxy-3-pyridyl 418 ″ NH S * 8 2-ethylthio-6- methoxy-3-pyridyl 419 ″ NH S * 9 2-ethylthio-6- methoxy-3-pyridyl 420 ″ NH S * 14 2-ethylthio-6- methoxy-3-pyridyl *: Single Bond  

TABLE 22 Compound No.

X Y Z n Het 421

O S * 1 2-(iso-propylthio)-6- methoxy-3-pyridyl 422 ″ O S * 2 2-(iso-propylthio)-6- methoxy-3-pyridyl 423 ″ O S * 3 2-(iso-propylthio)-6- methoxy-3-pyridyl 424 ″ O S * 4 2-(iso-propylthio)-6- methoxy-3-pyridyl 425 ″ O S * 5 2-(iso-propylthio)-6- methoxy-3-pyridyl 426 ″ O S * 6 2-(iso-propylthio)-6- methoxy-3-pyridyl 427 ″ O S * 7 2-(iso-propylthio)-6- methoxy-3-pyridyl 428 ″ O S * 8 2-(iso-propylthio)-6- methoxy-3-pyridyl 429 ″ O S * 9 2-(iso-propylthio)-6- methoxy-3-pyridyl 430 ″ O S * 14 2-(iso-propylthio)-6- methoxy-3-pyridyl 431 ″ S S * 1 2-(iso-propylthio)-6- methoxy-3-pyridyl 432 ″ S S * 2 2-(iso-propylthio)-6- methoxy-3-pyridyl 433 ″ S S * 3 2-(iso-propylthio)-6- methoxy-3-pyridyl 434 ″ S S * 4 2-(iso-propylthio)-6- methoxy-3-pyridyl 435 ″ S S * 5 2-(iso-propylthio)-6- methoxy-3-pyridyl 436 ″ S S * 6 2-(iso-propylthio)-6- methoxy-3-pyridyl 437 ″ S S * 7 2-(iso-propylthio)-6- methoxy-3-pyridyl 438 ″ S S * 8 2-(iso-propylthio)-6- methoxy-3-pyridyl 439 ″ S S * 9 2-(iso-propylthio)-6- methoxy-3-pyridyl 440 ″ S S * 14 2-(iso-propylthio)-6- methoxy-3-pyridyl *: Single Bond  

TABLE 23 Compound No.

X Y Z n Het 441

NH S * 1 2-(iso-propylthio)-6- methoxy-3-pyridyl 442 ″ NH S * 2 2-(iso-propylthio)-6- methoxy-3-pyridyl 443 ″ NH S * 3 2-(iso-propylthio)-6- methoxy-3-pyridyl 444 ″ NH S * 4 2-(iso-propylthio)-6- methoxy-3-pyridyl 445 ″ NH S * 5 2-(iso-propylthio)-6- methoxy-3-pyridyl 446 ″ NH S * 6 2-(iso-propylthio)-6- methoxy-3-pyridyl 447 ″ NH S * 7 2-(iso-propylthio)-6- methoxy-3-pyridyl 448 ″ NH S * 8 2-(iso-propylthio)-6- methoxy-3-pyridyl 449 ″ NH S * 9 2-(iso-propylthio)-6- methoxy-3-pyridyl 450 ″ NH S * 14 2-(iso-propylthio)-6- methoxy-3-pyridyl 451 ″ O S * 1 2-methylthio-6- methyl-3-pyridyl 452 ″ O S * 2 2-methylthio-6- methyl-3-pyridyl 453 ″ O S * 3 2-methylthio-6- methyl-3-pyridyl 454 ″ O S * 4 2-methylthio-6- methyl-3-pyridyl 455 ″ O S * 5 2-methylthio-6- methyl-3-pyridyl 456 ″ O S * 6 2-methylthio-6- methyl-3-pyridyl 457 ″ O S * 7 2-methylthio-6- methyl-3-pyridyl 458 ″ O S * 8 2-methylthio-6- methyl-3-pyridyl 459 ″ O S * 9 2-methylthio-6- methyl-3-pyridyl 460 ″ O S * 14 2-methylthio-6- methyl-3-pyridyl *: Single Bond  

TABLE 24 Compound No.

X Y Z n Het 461

S S * 1 2-methylthio-6- methyl-3-pyridyl 462 ″ S S * 2 2-methylthio-6- methyl-3-pyridyl 463 ″ S S * 3 2-methylthio-6- methyl-3-pyridyl 464 ″ S S * 4 2-methylthio-6- methyl-3-pyridyl 465 ″ S S * 5 2-methylthio-6- methyl-3-pyridyl 466 ″ S S * 6 2-methylthio-6- methyl-3-pyridyl 467 ″ S S * 7 2-methylthio-6- methyl-3-pyridyl 468 ″ S S * 8 2-methylthio-6- methyl-3-pyridyl 469 ″ S S * 9 2-methylthio-6- methyl-3-pyridyl 470 ″ S S * 14 2-methylthio-6- methyl-3-pyridyl 471 ″ NH S * 1 2-methylthio-6- methyl-3-pyridyl 472 ″ NH S * 2 2-methylthio-6- methyl-3-pyridyl 473 ″ NH S * 3 2-methylthio-6- methyl-3-pyridyl 474 ″ NH S * 4 2-methylthio-6- methyl-3-pyridyl 475 ″ NH S * 5 2-methylthio-6- methyl-3-pyridyl 476 ″ NH S * 6 2-methylthio-6- methyl-3-pyridyl 477 ″ NH S * 7 2-methylthio-6- methyl-3-pyridyl 478 ″ NH S * 8 2-methylthio-6- methyl-3-pyridyl 479 ″ NH S * 9 2-methylthio-6- methyl-3-pyridyl 480 ″ NH S * 14 2-methylthio-6- methyl-3-pyridyl *: Single Bond  

TABLE 25 Compound No.

X Y Z n Het 481

O S * 1 2-ethylthio-6-methyl- 3-pyridyl 482 ″ O S * 2 2-ethylthio-6-methyl- 3-pyridyl 483 ″ O S * 3 2-ethylthio-6-methyl- 3-pyridyl 484 ″ O S * 4 2-ethylthio-6-methyl- 3-pyridyl 485 ″ O S * 5 2-ethylthio-6-methyl- 3-pyridyl 486 ″ O S * 6 2-ethylthio-6-methyl- 3-pyridyl 487 ″ O S * 7 2-ethylthio-6-methyl- 3-pyridyl 488 ″ O S * 8 2-ethylthio-6-methyl- 3-pyridyl 489 ″ O S * 9 2-ethylthio-6-methyl- 3-pyridyl 490 ″ O S * 14 2-ethylthio-6-methyl- 3-pyridyl 491 ″ S S * 1 2-ethylthio-6-methyl- 3-pyridyl 492 ″ S S * 2 2-ethylthio-6-methyl- 3-pyridyl 493 ″ S S * 3 2-ethylthio-6-methyl- 3-pyridyl 494 ″ S S * 4 2-ethylthio-6-methyl- 3-pyridyl 495 ″ S S * 5 2-ethylthio-6-methyl- 3-pyridyl 496 ″ S S * 6 2-ethylthio-6-methyl- 3-pyridyl 497 ″ S S * 7 2-ethylthio-6-methyl- 3-pyridyl 498 ″ S S * 8 2-ethylthio-6-methyl- 3-pyridyl 499 ″ S S * 9 2-ethylthio-6-methyl- 3-pyridyl 500 ″ S S * 14 2-ethylthio-6-methyl- 3-pyridyl *: Single Bond  

TABLE 26 Compound No.

X Y Z n Het 501

NH S * 1 2-ethylthio-6- methyl-3-pyridyl 502 ″ NH S * 2 2-ethylthio-6- methyl-3-pyridyl 503 ″ NH S * 3 2-ethylthio-6- methyl-3-pyridyl 504 ″ NH S * 4 2-ethylthio-6- methyl-3-pyridyl 505 ″ NH S * 5 2-ethylthio-6- methyl-3-pyridyl 506 ″ NH S * 6 2-ethylthio-6- methyl-3-pyridyl 507 ″ NH S * 7 2-ethylthio-6- methyl-3-pyridyl 508 ″ NH S * 8 2-ethylthio-6- methyl-3-pyridyl 509 ″ NH S * 9 2-ethylthio-6- methyl-3-pyridyl 510 ″ NH S * 14 2-ethylthio-6- methyl-3-pyridyl 511 ″ O S * 1 2-(iso-propylthio)-6- methyl-3-pyridyl 512 ″ O S * 2 2-(iso-propylthio)-6- methyl-3-pyridyl 513 ″ O S * 3 2-(iso-propylthio)-6- methyl-3-pyridyl 514 ″ O S * 4 2-(iso-propylthio)-6- methyl-3-pyridyl 515 ″ O S * 5 2-(iso-propylthio)-6- methyl-3-pyridyl 516 ″ O S * 6 2-(iso-propylthio)-6- methyl-3-pyridyl 517 ″ O S * 7 2-(iso-propylthio)-6- methyl-3-pyridyl 518 ″ O S * 8 2-(iso-propylthio)-6- methyl-3-pyridyl 519 ″ O S * 9 2-(iso-propylthio)-6- methyl-3-pyridyl 520 ″ O S * 14 2-(iso-propylthio)-6- methyl-3-pyridyl *: Single Bond  

TABLE 27 Compound No.

X Y Z n Het 521

S S * 1 2-(iso-propylthio)- 6-methyl-3-pyridyl 522 ″ S S * 2 2-(iso-propylthio)- 6-methyl-3-pyridyl 523 ″ S S * 3 2-(iso-propylthio)- 6-methyl-3-pyridyl 524 ″ S S * 4 2-(iso-propylthio)- 6-methyl-3-pyridyl 525 ″ S S * 5 2-(iso-propylthio)- 6-methyl-3-pyridyl 526 ″ S S * 6 2-(iso-propylthio)- 6-methyl-3-pyridyl 527 ″ S S * 7 2-(iso-propylthio)- 6-methyl-3-pyridyl 528 ″ S S * 8 2-(iso-propylthio)- 6-methyl-3-pyridyl 529 ″ S S * 9 2-(iso-propylthio)- 6-methyl-3-pyridyl 530 ″ S S * 14 2-(iso-propylthio)- 6-methyl-3-pyridyl 531 ″ NH S * 1 2-(iso-propylthio)- 6-methyl-3-pyridyl 532 ″ NH S * 2 2-(iso-propylthio)- 6-methyl-3-pyridyl 533 ″ NH S * 3 2-(iso-propylthio)- 6-methyl-3-pyridyl 534 ″ NH S * 4 2-(iso-propylthio)- 6-methyl-3-pyridyl 535 ″ NH S * 5 2-(iso-propylthio)- 6-methyl-3-pyridyl 536 ″ NH S * 6 2-(iso-propylthio)- 6-methyl-3-pyridyl 537 ″ NH S * 7 2-(iso-propylthio)- 6-methyl-3-pyridyl 538 ″ NH S * 8 2-(iso-propylthio)- 6-methyl-3-pyridyl 539 ″ NH S * 9 2-(iso-propylthio)- 6-methyl-3-pyridyl 540 ″ NH S * 14 2-(iso-propylthio)- 6-methyl-3-pyridyl *: Single Bond  

TABLE 28 Compound No.

X Y Z n Het 541

O S * 1 2,6-dimethoxyl-3- pyridyl 542 ″ O S * 2 2,6-dimethoxyl-3- pyridyl 543 ″ O S * 3 2,6-dimethoxyl-3- pyridyl 544 ″ O S * 4 2,6-dimethoxyl-3- pyridyl 545 ″ O S * 5 2,6-dimethoxyl-3- pyridyl 546 ″ O S * 6 2,6-dimethoxyl-3- pyridyl 547 ″ O S * 7 2,6-dimethoxyl-3- pyridyl 548 ″ O S * 8 2,6-dimethoxyl-3- pyridyl 549 ″ O S * 9 2,6-dimethoxyl-3- pyridyl 550 ″ O S * 14 2,6-dimethoxyl-3- pyridyl 551 ″ S S * 1 2,6-dimethoxyl-3- pyridyl 552 ″ S S * 2 2,6-dimethoxyl-3- pyridyl 553 ″ S S * 3 2,6-dimethoxyl-3- pyridyl 554 ″ S S * 4 2,6-dimethoxyl-3- pyridyl 555 ″ S S * 5 2,6-dimethoxyl-3- pyridyl 556 ″ S S * 6 2,6-dimethoxyl-3- pyridyl 557 ″ S S * 7 2,6-dimethoxyl-3- pyridyl 558 ″ S S * 8 2,6-dimethoxyl-3- pyridyl 559 ″ S S * 9 2,6-dimethoxyl-3- pyridyl 560 ″ S S * 14 2,6-dimethoxyl-3- pyridyl *: Single Bond  

TABLE 29 Compound No.

X Y Z n Het 561

NH S * 1 2,6-dimethoxyl-3- pyridyl 562 ″ NH S * 2 2,6-dimethoxyl-3- pyridyl 563 ″ NH S * 3 2,6-dimethoxyl-3- pyridyl 564 ″ NH S * 4 2,6-dimethoxyl-3- pyridyl 565 ″ NH S * 5 2,6-dimethoxyl-3- pyridyl 566 ″ NH S * 6 2,6-dimethoxyl-3- pyridyl 567 ″ NH S * 7 2,6-dimethoxyl-3- pyridyl 568 ″ NH S * 8 2,6-dimethoxyl-3- pyridyl 569 ″ NH S * 9 2,6-dimethoxyl-3- pyridyl 570 ″ NH S * 14 2,6-dimethoxyl-3- pyridyl 571 ″ O S * 1 2-methoxy-6- methyl-3-pyridyl 572 ″ O S * 2 2-methoxy-6- methyl-3-pyridyl 573 ″ O S * 3 2-methoxy-6- methyl-3-pyridyl 574 ″ O S * 4 2-methoxy-6- methyl-3-pyridyl 575 ″ O S * 5 2-methoxy-6- methyl-3-pyridyl 576 ″ O S * 6 2-methoxy-6- methyl-3-pyridyl 577 ″ O S * 7 2-methoxy-6- methyl-3-pyridyl 578 ″ O S * 8 2-methoxy-6- methyl-3-pyridyl 579 ″ O S * 9 2-methoxy-6- methyl-3-pyridyl 580 ″ O S * 14 2-methoxy-6- methyl-3-pyridyl *: Single Bond  

TABLE 30 Compound No.

X Y Z n Het 581

S S * 1 2-methoxy-6- methyl-3-pyridyl 582 ″ S S * 2 2-methoxy-6- methyl-3-pyridyl 583 ″ S S * 3 2-methoxy-6- methyl-3-pyridyl 584 ″ S S * 4 2-methoxy-6- methyl-3-pyridyl 585 ″ S S * 5 2-methoxy-6- methyl-3-pyridyl 586 ″ S S * 6 2-methoxy-6- methyl-3-pyridyl 587 ″ S S * 7 2-methoxy-6- methyl-3-pyridyl 588 ″ S S * 8 2-methoxy-6- methyl-3-pyridyl 589 ″ S S * 9 2-methoxy-6- methyl-3-pyridyl 590 ″ S S * 14 2-methoxy-6- methyl-3-pyridyl 591 ″ NH S * 1 2-methoxy-6- methyl-3-pyridyl 592 ″ NH S * 2 2-methoxy-6- methyl-3-pyridyl 593 ″ NH S * 3 2-methoxy-6- methyl-3-pyridyl 594 ″ NH S * 4 2-methoxy-6- methyl-3-pyridyl 595 ″ NH S * 5 2-methoxy-6- methyl-3-pyridyl 596 ″ NH S * 6 2-methoxy-6- methyl-3-pyridyl 597 ″ NH S * 7 2-methoxy-6- methyl-3-pyridyl 598 ″ NH S * 8 2-methoxy-6- methyl-3-pyridyl 599 ″ NH S * 9 2-methoxy-6- methyl-3-pyridyl 600 ″ NH S * 14 2-methoxy-6- methyl-3-pyridyl *: Single Bond  

TABLE 31 Compound No.

X Y Z n Het 601

O S * 1 2-methyl-6-methyl- thio-3-pyridyl 602 ″ O S * 2 2-methyl-6-methyl- thio-3-pyridyl 603 ″ O S * 3 2-methyl-6-methyl- thio-3-pyridyl 604 ″ O S * 4 2-methyl-6-methyl- thio-3-pyridyl 605 ″ O S * 5 2-methyl-6-methyl- thio-3-pyridyl 606 ″ O S * 6 2-methyl-6-methyl- thio-3-pyridyl 607 ″ O S * 7 2-methyl-6-methyl- thio-3-pyridyl 608 ″ O S * 8 2-methyl-6-methyl- thio-3-pyridyl 609 ″ O S * 9 2-methyl-6-methyl- thio-3-pyridyl 610 ″ O S * 14 2-methyl-6-methyl- thio-3-pyridyl 611 ″ S S * 1 2-methyl-6-methyl- thio-3-pyridyl 612 ″ S S * 2 2-methyl-6-methyl- thio-3-pyridyl 613 ″ S S * 3 2-methyl-6-methyl- thio-3-pyridyl 614 ″ S S * 4 2-methyl-6-methyl- thio-3-pyridyl 615 ″ S S * 5 2-methyl-6-methyl- thio-3-pyridyl 616 ″ S S * 6 2-methyl-6-methyl- thio-3-pyridyl 617 ″ S S * 7 2-methyl-6-methyl- thio-3-pyridyl 618 ″ S S * 8 2-methyl-6-methyl- thio-3-pyridyl 619 ″ S S * 9 2-methyl-6-methyl- thio-3-pyridyl 620 ″ S S * 14 2-methyl-6-methyl- thio-3-pyridyl *: Single Bond  

TABLE 32 Compound No.

X Y Z n Het 621

NH S * 1 2-methyl-6-methyl- thio-3-pyridyl 622 ″ NH S * 2 2-methyl-6-methyl- thio-3-pyridyl 623 ″ NH S * 3 2-methyl-6-methyl- thio-3-pyridyl 624 ″ NH S * 4 2-methyl-6-methyl- thio-3-pyridyl 625 ″ NH S * 5 2-methyl-6-methyl- thio-3-pyridyl 626 ″ NH S * 6 2-methyl-6-methyl- thio-3-pyridyl 627 ″ NH S * 7 2-methyl-6-methyl- thio-3-pyridyl 628 ″ NH S * 8 2-methyl-6-methyl- thio-3-pyridyl 629 ″ NH S * 9 2-methyl-6-methyl- thio-3-pyridyl 630 ″ NH S * 14 2-methyl-6-methyl- thio-3-pyridyl 631 ″ O S * 1 2-methyl-6-ethyl- thio-3-pyridyl 632 ″ O S * 2 2-methyl-6-ethyl- thio-3-pyridyl 633 ″ O S * 3 2-methyl-6-ethyl- thio-3-pyridyl 634 ″ O S * 4 2-methyl-6-ethyl- thio-3-pyridyl 635 ″ O S * 5 2-methyl-6-ethyl- thio-3-pyridyl 636 ″ O S * 6 2-methyl-6-ethyl- thio-3-pyridyl 637 ″ O S * 7 2-methyl-6-ethyl- thio-3-pyridyl 638 ″ O S * 8 2-methyl-6-ethyl- thio-3-pyridyl 639 ″ O S * 9 2-methyl-6-ethyl- thio-3-pyridyl 640 ″ O S * 14 2-methyl-6-ethyl- thio-3-pyridyl *: Single Bond  

TABLE 33 Compound No.

X Y Z n Het 641

S S * 1 2-methyl-6-ethy- thio-3-pyridyl 642 ″ S S * 2 2-methyl-6-ethy- thio-3-pyridyl 643 ″ S S * 3 2-methyl-6-ethy- thio-3-pyridyl 644 ″ S S * 4 2-methyl-6-ethy- thio-3-pyridyl 645 ″ S S * 5 2-methyl-6-ethy- thio-3-pyridyl 646 ″ S S * 6 2-methyl-6-ethy- thio-3-pyridyl 647 ″ S S * 7 2-methyl-6-ethy- thio-3-pyridyl 648 ″ S S * 8 2-methyl-6-ethy- thio-3-pyridyl 649 ″ S S * 9 2-methyl-6-ethy- thio-3-pyridyl 650 ″ S S * 14 2-methyl-6-ethy- thio-3-pyridyl 651 ″ NH S * 1 2-methyl-6-ethy- thio-3-pyridyl 652 ″ NH S * 2 2-methyl-6-ethy- thio-3-pyridyl 653 ″ NH S * 3 2-methyl-6-ethy- thio-3-pyridyl 654 ″ NH S * 4 2-methyl-6-ethy- thio-3-pyridyl 655 ″ NH S * 5 2-methyl-6-ethy- thio-3-pyridyl 656 ″ NH S * 6 2-methyl-6-ethy- thio-3-pyridyl 657 ″ NH S * 7 2-methyl-6-ethy- thio-3-pyridyl 658 ″ NH S * 8 2-methyl-6-ethy- thio-3-pyridyl 659 ″ NH S * 9 2-methyl-6-ethy- thio-3-pyridyl 660 ″ NH S * 14 2-methyl-6-ethy- thio-3-pyridyl *: Single Bond  

TABLE 34 Compound No.

X Y Z n Het 661

O S * 1 2-methyl-6-(iso- propylthio)-3-pyridyl 662 ″ O S * 2 2-methyl-6-(iso- propylthio)-3-pyridyl 663 ″ O S * 3 2-methyl-6-(iso- propylthio)-3-pyridyl 664 ″ O S * 4 2-methyl-6-(iso- propylthio)-3-pyridyl 665 ″ O S * 5 2-methyl-6-(iso- propylthio)-3-pyridyl 666 ″ O S * 6 2-methyl-6-(iso- propylthio)-3-pyridyl 667 ″ O S * 7 2-methyl-6-(iso- propylthio)-3-pyridyl 668 ″ O S * 8 2-methyl-6-(iso- propylthio)-3-pyridyl 669 ″ O S * 9 2-methyl-6-(iso- propylthio)-3-pyridyl 670 ″ O S * 14 2-methyl-6-(iso- propylthio)-3-pyridyl 671 ″ S S * 1 2-methyl-6-(iso- propylthio)-3-pyridyl 672 ″ S S * 2 2-methyl-6-(iso- propylthio)-3-pyridyl 673 ″ S S * 3 2-methyl-6-(iso- propylthio)-3-pyridyl 674 ″ S S * 4 2-methyl-6-(iso- propylthio)-3-pyridyl 675 ″ S S * 5 2-methyl-6-(iso- propylthio)-3-pyridyl 676 ″ S S * 6 2-methyl-6-(iso- propylthio)-3-pyridyl 677 ″ S S * 7 2-methyl-6-(iso- propylthio)-3-pyridyl 678 ″ S S * 8 2-methyl-6-(iso- propylthio)-3-pyridyl 679 ″ S S * 9 2-methyl-6-(iso- propylthio)-3-pyridyl 680 ″ S S * 14 2-methyl-6-(iso- propylthio)-3-pyridyl *: Single Bond  

TABLE 35 Compound No.

X Y Z n Het 681

NH S * 1 2-methyl-6-(iso- propylthio)-3- pyridyl 682 ″ NH S * 2 2-methyl-6-(iso- propylthio)-3- pyridyl 683 ″ NH S * 3 2-methyl-6-(iso- propylthio)-3- pyridyl 684 ″ NH S * 4 2-methyl-6-(iso- propylthio)-3- pyridyl 685 ″ NH S * 5 2-methyl-6-(iso- propylthio)-3- pyridyl 686 ″ NH S * 6 2-methyl-6-(iso- propylthio)-3- pyridyl 687 ″ NH S * 7 2-methyl-6-(iso- propylthio)-3- pyridyl 688 ″ NH S * 8 2-methyl-6-(iso- propylthio)-3- pyridyl 689 ″ NH S * 9 2-methyl-6-(iso- propylthio)-3- pyridyl 690 ″ NH S * 14 2-methyl-6-(iso- propylthio)-3- pyridyl 691 ″ O S * 1 2-methyl-6- mehoxy-3-pyridyl 692 ″ O S * 2 2-methyl-6- mehoxy-3-pyridyl 693 ″ O S * 3 2-methyl-6- mehoxy-3-pyridyl 694 ″ O S * 4 2-methyl-6- mehoxy-3-pyridyl 695 ″ O S * 5 2-methyl-6- mehoxy-3-pyridyl 696 ″ O S * 6 2-methyl-6- mehoxy-3-pyridyl 697 ″ O S * 7 2-methyl-6- mehoxy-3-pyridyl 698 ″ O S * 8 2-methyl-6- mehoxy-3-pyridyl 699 ″ O S * 9 2-methyl-6- mehoxy-3-pyridyl 700 ″ O S * 14 2-methyl-6- mehoxy-3-pyridyl *: Single Bond  

TABLE 36 Compound No.

X Y Z n Het 701

S S * 1 2-methyl-6- mehoxy-3-pyridyl 702 ″ S S * 2 2-methyl-6- mehoxy-3-pyridyl 703 ″ S S * 3 2-methyl-6- mehoxy-3-pyridyl 704 ″ S S * 4 2-methyl-6- mehoxy-3-pyridyl 705 ″ S S * 5 2-methyl-6- mehoxy-3-pyridyl 706 ″ S S * 6 2-methyl-6- mehoxy-3-pyridyl 707 ″ S S * 7 2-methyl-6- mehoxy-3-pyridyl 708 ″ S S * 8 2-methyl-6- mehoxy-3-pyridyl 709 ″ S S * 9 2-methyl-6- mehoxy-3-pyridyl 710 ″ S S * 14 2-methyl-6- mehoxy-3-pyridyl 711 ″ NH S * 1 2-methyl-6- mehoxy-3-pyridyl 712 ″ NH S * 2 2-methyl-6- mehoxy-3-pyridyl 713 ″ NH S * 3 2-methyl-6- mehoxy-3-pyridyl 714 ″ NH S * 4 2-methyl-6- mehoxy-3-pyridyl 715 ″ NH S * 5 2-methyl-6- mehoxy-3-pyridyl 716 ″ NH S * 6 2-methyl-6- mehoxy-3-pyridyl 717 ″ NH S * 7 2-methyl-6- mehoxy-3-pyridyl 718 ″ NH S * 8 2-methyl-6- mehoxy-3-pyridyl 719 ″ NH S * 9 2-methyl-6- mehoxy-3-pyridyl 720 ″ NH S * 14 2-methyl-6- mehoxy-3-pyridyl *: Single Bond  

TABLE 37 Compound No.

X Y Z n Het 721

O S * 1 2,6-dimethyl-3-pyridyl 722 ″ O S * 2 2,6-dimethyl-3-pyridyl 723 ″ O S * 3 2,6-dimethyl-3-pyridyl 724 ″ O S * 4 2,6-dimethyl-3-pyridyl 725 ″ O S * 5 2,6-dimethyl-3-pyridyl 726 ″ O S * 6 2,6-dimethyl-3-pyridyl 727 ″ O S * 7 2,6-dimethyl-3-pyridyl 728 ″ O S * 8 2,6-dimethyl-3-pyridyl 729 ″ O S * 9 2,6-dimethyl-3-pyridyl 730 ″ O S * 14 2,6-dimethyl-3-pyridyl 731 ″ S S * 1 2,6-dimethyl-3-pyridyl 732 ″ S S * 2 2,6-dimethyl-3-pyridyl 733 ″ S S * 3 2,6-dimethyl-3-pyridyl 734 ″ S S * 4 2,6-dimethyl-3-pyridyl 735 ″ S S * 5 2,6-dimethyl-3-pyridyl 736 ″ S S * 6 2,6-dimethyl-3-pyridyl 737 ″ S S * 7 2,6-dimethyl-3-pyridyl 738 ″ S S * 8 2,6-dimethyl-3-pyridyl 739 ″ S S * 9 2,6-dimethyl-3-pyridyl 740 ″ S S * 14 2,6-dimethyl-3-pyridyl *: Single Bond  

TABLE 38 Compound No.

X Y Z n Het 741

NH S * 1 2,6-dimethyl-3- pyridyl 742 ″ NH S * 2 2,6-dimethyl-3- pyridyl 743 ″ NH S * 3 2,6-dimethyl-3- pyridyl 744 ″ NH S * 4 2,6-dimethyl-3- pyridyl 745 ″ NH S * 5 2,6-dimethyl-3- pyridyl 746 ″ NH S * 6 2,6-dimethyl-3- pyridyl 747 ″ NH S * 7 2,6-dimethyl-3- pyridyl 748 ″ NH S * 8 2,6-dimethyl-3- pyridyl 749 ″ NH S * 9 2,6-dimethyl-3- pyridyl 750 ″ NH S * 14 2,6-dimethyl-3- pyridyl 751 ″ O S * 1 2,6-dimethyl-3- pyridyl 752 ″ O S * 2 2,6-dimethyl-3- pyridyl 753 ″ O S * 3 2,6-dimethyl-3- pyridyl 754 ″ O S * 4 2,6-dimethyl-3- pyridyl 755 ″ O S * 5 2,6-dimethyl-3- pyridyl 756 ″ O S * 6 2,6-dimethyl-3- pyridyl 757 ″ O S * 7 2,6-dimethyl-3- pyridyl 758 ″ O S * 8 2,6-dimethyl-3- pyridyl 759 ″ O S * 9 2,6-dimethyl-3- pyridyl 760 ″ O S * 14 2,6-dimethyl-3- pyridyl *: Single Bond  

TABLE 39 Compound No.

X Y Z n Het 761

S S * 1 2,6-diethyl-3- pyridyl 762 ″ S S * 2 2,6-diethyl-3- pyridyl 763 ″ S S * 3 2,6-diethyl-3- pyridyl 764 ″ S S * 4 2,6-diethyl-3- pyridyl 765 ″ S S * 5 2,6-diethyl-3- pyridyl 766 ″ S S * 6 2,6-diethyl-3- pyridyl 767 ″ S S * 7 2,6-diethyl-3- pyridyl 768 ″ S S * 8 2,6-diethyl-3- pyridyl 769 ″ S S * 9 2,6-diethyl-3- pyridyl 770 ″ S S * 14 2,6-diethyl-3- pyridyl 771 ″ NH S * 1 2,6-diethyl-3- pyridyl 772 ″ NH S * 2 2,6-diethyl-3- pyridyl 773 ″ NH S * 3 2,6-diethyl-3- pyridyl 774 ″ NH S * 4 2,6-diethyl-3- pyridyl 775 ″ NH S * 5 2,6-diethyl-3- pyridyl 776 ″ NH S * 6 2,6-diethyl-3- pyridyl 777 ″ NH S * 7 2,6-diethyl-3- pyridyl 778 ″ NH S * 8 2,6-diethyl-3- pyridyl 779 ″ NH S * 9 2,6-diethyl-3- pyridyl 780 ″ NH S * 14 2,6-diethyl-3- pyridyl *: Single Bond  

TABLE 40 Compound No.

X Y Z n Het 781

O S * 1 2,4-bismethylthio- 6-methyl-3-pyridyl 782 ″ O S * 2 2,4-bismethylthio- 6-methyl-3-pyridyl 783 ″ O S * 3 2,4-bismethylthio- 6-methyl-3-pyridyl 784 ″ O S * 4 2,4-bismethylthio- 6-methyl-3-pyridyl 785 ″ O S * 5 2,4-bismethylthio- 6-methyl-3-pyridyl 786 ″ O S * 6 2,4-bismethylthio- 6-methyl-3-pyridyl 787 ″ O S * 7 2,4-bismethylthio- 6-methyl-3-pyridyl 788 ″ O S * 8 2,4-bismethylthio- 6-methyl-3-pyridyl 789 ″ O S * 9 2,4-bismethylthio- 6-methyl-3-pyridyl 790 ″ O S * 14 2,4-bismethylthio- 6-methyl-3-pyridyl 791 ″ S S * 1 2,4-bismethylthio- 6-methyl-3-pyridyl 792 ″ S S * 2 2,4-bismethylthio- 6-methyl-3-pyridyl 793 ″ S S * 3 2,4-bismethylthio- 6-methyl-3-pyridyl 794 ″ S S * 4 2,4-bismethylthio- 6-methyl-3-pyridyl 795 ″ S S * 5 2,4-bismethylthio- 6-methyl-3-pyridyl 796 ″ S S * 6 2,4-bismethylthio- 6-methyl-3-pyridyl 797 ″ S S * 7 2,4-bismethylthio- 6-methyl-3-pyridyl 798 ″ S S * 8 2,4-bismethylthio- 6-methyl-3-pyridyl 799 ″ S S * 9 2,4-bismethylthio- 6-methyl-3-pyridyl 800 ″ S S * 14 2,4-bismethylthio- 6-methyl-3-pyridyl *: Single Bond  

TABLE 41 Compound No.

X Y Z n Het 801

NH S * 1 2,4-bismethylthio- 6-methyl-3-pyridyl 802 ″ NH S * 2 2,4-bismethylthio- 6-methyl-3-pyridyl 803 ″ NH S * 3 2,4-bismethylthio- 6-methyl-3-pyridyl 804 ″ NH S * 4 2,4-bismethylthio- 6-methyl-3-pyridyl 805 ″ NH S * 5 2,4-bismethylthio- 6-methyl-3-pyridyl 806 ″ NH S * 6 2,4-bismethylthio- 6-methyl-3-pyridyl 807 ″ NH S * 7 2,4-bismethylthio- 6-methyl-3-pyridyl 808 ″ NH S * 8 2,4-bismethylthio- 6-methyl-3-pyridyl 809 ″ NH S * 9 2,4-bismethylthio- 6-methyl-3-pyridyl 810 ″ NH S * 14 2,4-bismethylthio- 6-methyl-3-pyridyl 811 ″ O S * 1 2,4-bisethylthio-6- methyl-3-pyridyl 812 ″ O S * 2 2,4-bisethylthio-6- methyl-3-pyridyl 813 ″ O S * 3 2,4-bisethylthio-6- methyl-3-pyridyl 814 ″ O S * 4 2,4-bisethylthio-6- methyl-3-pyridyl 815 ″ O S * 5 2,4-bisethylthio-6- methyl-3-pyridyl 816 ″ O S * 6 2,4-bisethylthio-6- methyl-3-pyridyl 817 ″ O S * 7 2,4-bisethylthio-6- methyl-3-pyridyl 818 ″ O S * 8 2,4-bisethylthio-6- methyl-3-pyridyl 819 ″ O S * 9 2,4-bisethylthio-6- methyl-3-pyridyl 820 ″ O S * 14 2,4-bisethylthio-6- methyl-3-pyridyl *: Single Bond  

TABLE 42 Compound No.

X Y Z n Het 821

S S * 1 2,4-bisethylthio-6- methyl-3-pyridyl 822 ″ S S * 2 2,4-bisethylthio-6- methyl-3-pyridyl 823 ″ S S * 3 2,4-bisethylthio-6- methyl-3-pyridyl 824 ″ S S * 4 2,4-bisethylthio-6- methyl-3-pyridyl 825 ″ S S * 5 2,4-bisethylthio-6- methyl-3-pyridyl 826 ″ S S * 6 2,4-bisethylthio-6- methyl-3-pyridyl 827 ″ S S * 7 2,4-bisethylthio-6- methyl-3-pyridyl 828 ″ S S * 8 2,4-bisethylthio-6- methyl-3-pyridyl 829 ″ S S * 9 2,4-bisethylthio-6- methyl-3-pyridyl 830 ″ S S * 14 2,4-bisethylthio-6- methyl-3-pyridyl 831 ″ NH S * 1 2,4-bisethylthio-6- methyl-3-pyridyl 832 ″ NH S * 2 2,4-bisethylthio-6- methyl-3-pyridyl 833 ″ NH S * 3 2,4-bisethylthio-6- methyl-3-pyridyl 834 ″ NH S * 4 2,4-bisethylthio-6- methyl-3-pyridyl 835 ″ NH S * 5 2,4-bisethylthio-6- methyl-3-pyridyl 836 ″ NH S * 6 2,4-bisethylthio-6- methyl-3-pyridyl 837 ″ NH S * 7 2,4-bisethylthio-6- methyl-3-pyridyl 838 ″ NH S * 8 2,4-bisethylthio-6- methyl-3-pyridyl 839 ″ NH S * 9 2,4-bisethylthio-6- methyl-3-pyridyl 840 ″ NH S * 14 2,4-bisethylthio-6- methyl-3-pyridyl *: Single Bond  

TABLE 43 Compound No.

X Y Z n Het 841

O S * 1 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 842 ″ O S * 2 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 843 ″ O S * 3 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 844 ″ O S * 4 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 845 ″ O S * 5 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 846 ″ O S * 6 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 847 ″ O S * 7 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 848 ″ O S * 8 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 849 ″ O S * 9 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 850 ″ O S * 14 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 851 ″ S S * 1 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 852 ″ S S * 2 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 853 ″ S S * 3 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 854 ″ S S * 4 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 855 ″ S S * 5 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 856 ″ S S * 6 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 857 ″ S S * 7 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 858 ″ S S * 8 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 859 ″ S S * 9 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 860 ″ S S * 14 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl *: Single Bond  

TABLE 44 Compound No.

X Y Z n Het 861

NH S * 1 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 862 ″ NH S * 2 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 863 ″ NH S * 3 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 864 ″ NH S * 4 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 865 ″ NH S * 5 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 866 ″ NH S * 6 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 867 ″ NH S * 7 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 868 ″ NH S * 8 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 869 ″ NH S * 9 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 870 ″ NH S * 14 2,4-bis(iso-propyl- thio)-6-methyl-3- pyridyl 871 ″ O S * 1 2,4-dimethoxy-6- methyl-3-pyridyl 872 ″ O S * 2 2,4-dimethoxy-6- methyl-3-pyridyl 873 ″ O S * 3 2,4-dimethoxy-6- methyl-3-pyridyl 874 ″ O S * 4 2,4-dimethoxy-6- methyl-3-pyridyl 875 ″ O S * 5 2,4-dimethoxy-6- methyl-3-pyridyl 876 ″ O S * 6 2,4-dimethoxy-6- methyl-3-pyridyl 877 ″ O S * 7 2,4-dimethoxy-6- methyl-3-pyridyl 878 ″ O S * 8 2,4-dimethoxy-6- methyl-3-pyridyl 879 ″ O S * 9 2,4-dimethoxy-6- methyl-3-pyridyl 880 ″ O S * 14 2,4-dimethoxy-6- methyl-3-pyridyl *: Single Bond  

TABLE 45 Compound No.

X Y Z n Het 881

S S * 1 2,4-dimethoxy-6- methyl-3-pyridyl 882 ″ S S * 2 2,4-dimethoxy-6- methyl-3-pyridyl 883 ″ S S * 3 2,4-dimethoxy-6- methyl-3-pyridyl 884 ″ S S * 4 2,4-dimethoxy-6- methyl-3-pyridyl 885 ″ S S * 5 2,4-dimethoxy-6- methyl-3-pyridyl 886 ″ S S * 6 2,4-dimethoxy-6- methyl-3-pyridyl 887 ″ S S * 7 2,4-dimethoxy-6- methyl-3-pyridyl 888 ″ S S * 8 2,4-dimethoxy-6- methyl-3-pyridyl 889 ″ S S * 9 2,4-dimethoxy-6- methyl-3-pyridyl 890 ″ S S * 14 2,4-dimethoxy-6- methyl-3-pyridyl 891 ″ NH S * 1 2,4-dimethoxy-6- methyl-3-pyridyl 892 ″ NH S * 2 2,4-dimethoxy-6- methyl-3-pyridyl 893 ″ NH S * 3 2,4-dimethoxy-6- methyl-3-pyridyl 894 ″ NH S * 4 2,4-dimethoxy-6- methyl-3-pyridyl 895 ″ NH S * 5 2,4-dimethoxy-6- methyl-3-pyridyl 896 ″ NH S * 6 2,4-dimethoxy-6- methyl-3-pyridyl 897 ″ NH S * 7 2,4-dimethoxy-6- methyl-3-pyridyl 898 ″ NH S * 8 2,4-dimethoxy-6- methyl-3-pyridyl 899 ″ NH S * 9 2,4-dimethoxy-6- methyl-3-pyridyl 900 ″ NH S * 14 2,4-dimethoxy-6- methyl-3-pyridyl *: Single Bond  

TABLE 46 Compound No.

X Y Z n Het 901

O S * 1 2,4,6-trimethyl-3-pyridyl 902 ″ O S * 2 2,4,6-trimethyl-3-pyridyl 903 ″ O S * 3 2,4,6-trimethyl-3-pyridyl 904 ″ O S * 4 2,4,6-trimethyl-3-pyridyl 905 ″ O S * 5 2,4,6-trimethyl-3-pyridyl 906 ″ O S * 6 2,4,6-trimethyl-3-pyridyl 907 ″ O S * 7 2,4,6-trimethyl-3-pyridyl 908 ″ O S * 8 2,4,6-trimethyl-3-pyridyl 909 ″ O S * 9 2,4,6-trimethyl-3-pyridyl 910 ″ O S * 14 2,4,6-trimethyl-3-pyridyl 911 ″ S S * 1 2,4,6-trimethyl-3-pyridyl 912 ″ S S * 2 2,4,6-trimethyl-3-pyridyl 913 ″ S S * 3 2,4,6-trimethyl-3-pyridyl 914 ″ S S * 4 2,4,6-trimethyl-3-pyridyl 915 ″ S S * 5 2,4,6-trimethyl-3-pyridyl 916 ″ S S * 6 2,4,6-trimethyl-3-pyridyl 917 ″ S S * 7 2,4,6-trimethyl-3-pyridyl 918 ″ S S * 8 2,4,6-trimethyl-3-pyridyl 919 ″ S S * 9 2,4,6-trimethyl-3-pyridyl 920 ″ S S * 14 2,4,6-trimethyl-3-pyridyl *Single Bond  

TABLE 47 Compound No.

X Y Z n Het 921

NH S * 1 2,4,6-trimethyl-3-pyridyl 922 ″ NH S * 2 2,4,6-trimethyl-3-pyridyl 923 ″ NH S * 3 2,4,6-trimethyl-3-pyridyl 924 ″ NH S * 4 2,4,6-trimethyl-3-pyridyl 925 ″ NH S * 5 2,4,6-trimethyl-3-pyridyl 926 ″ NH S * 6 2,4,6-trimethyl-3-pyridyl 927 ″ NH S * 7 2,4,6-trimethyl-3-pyridyl 928 ″ NH S * 8 2,4,6-trimethyl-3-pyridyl 929 ″ NH S * 9 2,4,6-trimethyl-3-pyridyl 930 ″ NH S * 14 2,4,6-trimethyl-3-pyridyl 931 ″ O S * 1 4-ethyl-2,6-dimethyl-3-pyridyl 932 ″ O S * 2 4-ethyl-2,6-dimethyl-3-pyridyl 933 ″ O S * 3 4-ethyl-2,6-dimethyl-3-pyridyl 934 ″ O S * 4 4-ethyl-2,6-dimethyl-3-pyridyl 935 ″ O S * 5 4-ethyl-2,6-dimethyl-3-pyridyl 936 ″ O S * 6 4-ethyl-2,6-dimethyl-3-pyridyl 937 ″ O S * 7 4-ethyl-2,6-dimethyl-3-pyridyl 938 ″ O S * 8 4-ethyl-2,6-dimethyl-3-pyridyl 939 ″ O S * 9 4-ethyl-2,6-dimethyl-3-pyridyl 940 ″ O S * 14 4-ethyl-2,6-dimethyl-3-pyridyl *Single Bond  

TABLE 48 Compound No.

X Y Z n Het 941

S S * 1 4-ethyl-2,6-dimethyl-3-pyridyl 942 ″ S S * 2 4-ethyl-2,6-dimethyl-3-pyridyl 943 ″ S S * 3 4-ethyl-2,6-dimethyl-3-pyridyl 944 ″ S S * 4 4-ethyl-2,6-dimethyl-3-pyridyl 945 ″ S S * 5 4-ethyl-2,6-dimethyl-3-pyridyl 946 ″ S S * 6 4-ethyl-2,6-dimethyl-3-pyridyl 947 ″ S S * 7 4-ethyl-2,6-dimethyl-3-pyridyl 948 ″ S S * 8 4-ethyl-2,6-dimethyl-3-pyridyl 949 ″ S S * 9 4-ethyl-2,6-dimethyl-3-pyridyl 950 ″ S S * 14 4-ethyl-2,6-dimethyl-3-pyridyl 951 ″ NH S * 1 4-ethyl-2,6-dimethyl-3-pyridyl 952 ″ NH S * 2 4-ethyl-2,6-dimethyl-3-pyridyl 953 ″ NH S * 3 4-ethyl-2,6-dimethyl-3-pyridyl 954 ″ NH S * 4 4-ethyl-2,6-dimethyl-3-pyridyl 955 ″ NH S * 5 4-ethyl-2,6-dimethyl-3-pyridyl 956 ″ NH S * 6 4-ethyl-2,6-dimethyl-3-pyridyl 957 ″ NH S * 7 4-ethyl-2,6-dimethyl-3-pyridyl 958 ″ NH S * 8 4-ethyl-2,6-dimethyl-3-pyridyl 959 ″ NH S * 9 4-ethyl-2,6-dimethyl-3-pyridyl 960 ″ NH S * 14 4-ethyl-2,6-dimethyl-3-pyridyl *Single Bond  

TABLE 49 Compound No.

X Y Z n Het 961

O S * 1 2,4-dichloro-6-methyl-3-pyridyl 962 ″ O S * 2 2,4-dichloro-6-methyl-3-pyridyl 963 ″ O S * 3 2,4-dichloro-6-methyl-3-pyridyl 964 ″ O S * 4 2,4-dichloro-6-methyl-3-pyridyl 965 ″ O S * 5 2,4-dichloro-6-methyl-3-pyridyl 966 ″ O S * 6 2,4-dichloro-6-methyl-3-pyridyl 967 ″ O S * 7 2,4-dichloro-6-methyl-3-pyridyl 968 ″ O S * 8 2,4-dichloro-6-methyl-3-pyridyl 969 ″ O S * 9 2,4-dichloro-6-methyl-3-pyridyl 970 ″ O S * 14 2,4-dichloro-6-methyl-3-pyridyl 971 ″ S S * 1 2,4-dichloro-6-methyl-3-pyridyl 972 ″ S S * 2 2,4-dichloro-6-methyl-3-pyridyl 973 ″ S S * 3 2,4-dichloro-6-methyl-3-pyridyl 974 ″ S S * 4 2,4-dichloro-6-methyl-3-pyridyl 975 ″ S S * 5 2,4-dichloro-6-methyl-3-pyridyl 976 ″ S S * 6 2,4-dichloro-6-methyl-3-pyridyl 977 ″ S S * 7 2,4-dichloro-6-methyl-3-pyridyl 978 ″ S S * 8 2,4-dichloro-6-methyl-3-pyridyl 979 ″ S S * 9 2,4-dichloro-6-methyl-3-pyridyl 980 ″ S S * 14 2,4-dichloro-6-methyl-3-pyridyl *Single Bond  

TABLE 50 Compound No.

X Y Z n Het 981

NH S * 1 2,4-dichloro-6-methyl-3-pyridyl 982 ″ NH S * 2 2,4-dichloro-6-methyl-3-pyridyl 983 ″ NH S * 3 2,4-dichloro-6-methyl-3-pyridyl 984 ″ NH S * 4 2,4-dichloro-6-methyl-3-pyridyl 985 ″ NH S * 5 2,4-dichloro-6-methyl-3-pyridyl 986 ″ NH S * 6 2,4-dichloro-6-methyl-3-pyridyl 987 ″ NH S * 7 2,4-dichloro-6-methyl-3-pyridyl 988 ″ NH S * 8 2,4-dichloro-6-methyl-3-pyridyl 989 ″ NH S * 9 2,4-dichloro-6-methyl-3-pyridyl 990 ″ NH S * 14 2,4-dichloro-6-methyl-3-pyridyl 991 ″ O S * 1 4,6-bismethylthio-5-pyrimidyl 992 ″ O S * 2 4,6-bismethylthio-5-pyrimidyl 993 ″ O S * 3 4,6-bismethylthio-5-pyrimidyl 994 ″ O S * 4 4,6-bismethylthio-5-pyrimidyl 995 ″ O S * 5 4,6-bismethylthio-5-pyrimidyl 996 ″ O S * 6 4,6-bismethylthio-5-pyrimidyl 997 ″ O S * 7 4,6-bismethylthio-5-pyrimidyl 998 ″ O S * 8 4,6-bismethylthio-5-pyrimidyl 999 ″ O S * 9 4,6-bismethylthio-5-pyrimidyl 1000  ″ O S * 14 4,6-bismethylthio-5-pyrimidyl *Single Bond  

TABLE 51 Compound No.

X Y Z n Het 1001

S S * 1 4,6-bismethylthio-5-pyrimidyl 1002 ″ S S * 2 4,6-bismethylthio-5-pyrimidyl 1003 ″ S S * 3 4,6-bismethylthio-5-pyrimidyl 1004 ″ S S * 4 4,6-bismethylthio-5-pyrimidyl 1005 ″ S S * 5 4,6-bismethylthio-5-pyrimidyl 1006 ″ S S * 6 4,6-bismethylthio-5-pyrimidyl 1007 ″ S S * 7 4,6-bismethylthio-5-pyrimidyl 1008 ″ S S * 8 4,6-bismethylthio-5-pyrimidyl 1009 ″ S S * 9 4,6-bismethylthio-5-pyrimidyl 1010 ″ S S * 14 4,6-bismethylthio-5-pyrimidyl 1011 ″ NH S * 1 4,6-bismethylthio-5-pyrimidyl 1012 ″ NH S * 2 4,6-bismethylthio-5-pyrimidyl 1013 ″ NH S * 3 4,6-bismethylthio-5-pyrimidyl 1014 ″ NH S * 4 4,6-bismethylthio-5-pyrimidyl 1015 ″ NH S * 5 4,6-bismethylthio-5-pyrimidyl 1016 ″ NH S * 6 4,6-bismethylthio-5-pyrimidyl 1017 ″ NH S * 7 4,6-bismethylthio-5-pyrimidyl 1018 ″ NH S * 8 4,6-bismethylthio-5-pyrimidyl 1019 ″ NH S * 9 4,6-bismethylthio-5-pyrimidyl 1020 ″ NH S * 14 4,6-bismethylthio-5-pyrimidyl *Single Bond  

TABLE 52 Compound No.

X Y Z n Het 1021

O S * 1 4,6-bisethylthio-5-pyrimidyl 1022 ″ O S * 2 4,6-bisethylthio-5-pyrimidyl 1023 ″ O S * 3 4,6-bisethylthio-5-pyrimidyl 1024 ″ O S * 4 4,6-bisethylthio-5-pyrimidyl 1025 ″ O S * 5 4,6-bisethylthio-5-pyrimidyl 1026 ″ O S * 6 4,6-bisethylthio-5-pyrimidyl 1027 ″ O S * 7 4,6-bisethylthio-5-pyrimidyl 1028 ″ O S * 8 4,6-bisethylthio-5-pyrimidyl 1029 ″ O S * 9 4,6-bisethylthio-5-pyrimidyl 1030 ″ O S * 14 4,6-bisethylthio-5-pyrimidyl 1031 ″ S S * 1 4,6-bisethylthio-5-pyrimidyl 1032 ″ S S * 2 4,6-bisethylthio-5-pyrimidyl 1033 ″ S S * 3 4,6-bisethylthio-5-pyrimidyl 1034 ″ S S * 4 4,6-bisethylthio-5-pyrimidyl 1035 ″ S S * 5 4,6-bisethylthio-5-pyrimidyl 1036 ″ S S * 6 4,6-bisethylthio-5-pyrimidyl 1037 ″ S S * 7 4,6-bisethylthio-5-pyrimidyl 1038 ″ S S * 8 4,6-bisethylthio-5-pyrimidyl 1039 ″ S S * 9 4,6-bisethylthio-5-pyrimidyl 1040 ″ S S * 14 4,6-bisethylthio-5-pyrimidyl *Single Bond  

TABLE 53 Compound No.

X Y Z n Het 1041

NH S * 1 4,6-bisethylthio-5-pyrimidyl 1042 ″ NH S * 2 4,6-bisethylthio-5-pyrimidyl 1043 ″ NH S * 3 4,6-bisethylthio-5-pyrimidyl 1044 ″ NH S * 4 4,6-bisethylthio-5-pyrimidyl 1045 ″ NH S * 5 4,6-bisethylthio-5-pyrimidyl 1046 ″ NH S * 6 4,6-bisethylthio-5-pyrimidyl 1047 ″ NH S * 7 4,6-bisethylthio-5-pyrimidyl 1048 ″ NH S * 8 4,6-bisethylthio-5-pyrimidyl 1049 ″ NH S * 9 4,6-bisethylthio-5-pyrimidyl 1050 ″ NH S * 14 4,6-bisethylthio-5-pyrimidyl 1051 ″ O S * 1 4,6-bis(iso-propylthio)-5-pyrimidyl 1052 ″ O S * 2 4,6-bis(iso-propylthio)-5-pyrimidyl 1053 ″ O S * 3 4,6-bis(iso-propylthio)-5-pyrimidyl 1054 ″ O S * 4 4,6-bis(iso-propylthio)-5-pyrimidyl 1055 ″ O S * 5 4,6-bis(iso-propylthio)-5-pyrimidyl 1056 ″ O S * 6 4,6-bis(iso-propylthio)-5-pyrimidyl 1057 ″ O S * 7 4,6-bis(iso-propylthio)-5-pyrimidyl 1058 ″ O S * 8 4,6-bis(iso-propylthio)-5-pyrimidyl 1059 ″ O S * 9 4,6-bis(iso-propylthio)-5-pyrimidyl 1060 ″ O S * 14 4,6-bis(iso-propylthio)-5-pyrimidyl *Single Bond  

TABLE 54 Compound No.

X Y Z n Het 1061

S S * 1 4,6-bis(iso-propylthio)-5-pyrimidyl 1062 ″ S S * 2 4,6-bis(iso-propylthio)-5-pyrimidyl 1063 ″ S S * 3 4,6-bis(iso-propylthio)-5-pyrimidyl 1064 ″ S S * 4 4,6-bis(iso-propylthio)-5-pyrimidyl 1065 ″ S S * 5 4,6-bis(iso-propylthio)-5-pyrimidyl 1066 ″ S S * 6 4,6-bis(iso-propylthio)-5-pyrimidyl 1067 ″ S S * 7 4,6-bis(iso-propylthio)-5-pyrimidyl 1068 ″ S S * 8 4,6-bis(iso-propylthio)-5-pyrimidyl 1069 ″ S S * 9 4,6-bis(iso-propylthio)-5-pyrimidyl 1070 ″ S S * 14 4,6-bis(iso-propylthio)-5-pyrimidyl 1071 ″ NH S * 1 4,6-bis(iso-propylthio)-5-pyrimidyl 1072 ″ NH S * 2 4,6-bis(iso-propylthio)-5-pyrimidyl 1073 ″ NH S * 3 4,6-bis(iso-propylthio)-5-pyrimidyl 1074 ″ NH S * 4 4,6-bis(iso-propylthio)-5-pyrimidyl 1075 ″ NH S * 5 4,6-bis(iso-propylthio)-5-pyrimidyl 1076 ″ NH S * 6 4,6-bis(iso-propylthio)-5-pyrimidyl 1077 ″ NH S * 7 4,6-bis(iso-propylthio)-5-pyrimidyl 1078 ″ NH S * 8 4,6-bis(iso-propylthio)-5-pyrimidyl 1079 ″ NH S * 9 4,6-bis(iso-propylthio)-5-pyrimidyl 1080 ″ NH S * 14 4,6-bis(iso-propylthio)-5-pyrimidyl *Single Bond  

TABLE 55 Compound No.

X Y Z n Het 1081

O S * 1 4,6-dimethoxy-5-pyrimidyl 1082 ″ O S * 2 4,6-dimethoxy-5-pyrimidyl 1083 ″ O S * 3 4,6-dimethoxy-5-pyrimidyl 1084 ″ O S * 4 4,6-dimethoxy-5-pyrimidyl 1085 ″ O S * 5 4,6-dimethoxy-5-pyrimidyl 1086 ″ O S * 6 4,6-dimethoxy-5-pyrimidyl 1087 ″ O S * 7 4,6-dimethoxy-5-pyrimidyl 1088 ″ O S * 8 4,6-dimethoxy-5-pyrimidyl 1089 ″ O S * 9 4,6-dimethoxy-5-pyrimidyl 1090 ″ O S * 14 4,6-dimethoxy-5-pyrimidyl 1091 ″ S S * 1 4,6-dimethoxy-5-pyrimidyl 1092 ″ S S * 2 4,6-dimethoxy-5-pyrimidyl 1093 ″ S S * 3 4,6-dimethoxy-5-pyrimidyl 1094 ″ S S * 4 4,6-dimethoxy-5-pyrimidyl 1095 ″ S S * 5 4,6-dimethoxy-5-pyrimidyl 1096 ″ S S * 6 4,6-dimethoxy-5-pyrimidyl 1097 ″ S S * 7 4,6-dimethoxy-5-pyrimidyl 1098 ″ S S * 8 4,6-dimethoxy-5-pyrimidyl 1099 ″ S S * 9 4,6-dimethoxy-5-pyrimidyl 1100 ″ S S * 14 4,6-dimethoxy-5-pyrimidyl *Single Bond  

TABLE 56 Compound No.

X Y Z n Het 1101

NH S * 1 4,6-dichloro-2-methyl-5-pyrimidyl 1102 ″ NH S * 2 4,6-dichloro-2-methyl-5-pyrimidyl 1103 ″ NH S * 3 4,6-dichloro-2-methyl-5-pyrimidyl 1104 ″ NH S * 4 4,6-dichloro-2-methyl-5-pyrimidyl 1105 ″ NH S * 5 4,6-dichloro-2-methyl-5-pyrimidyl 1106 ″ NH S * 6 4,6-dichloro-2-methyl-5-pyrimidyl 1107 ″ NH S * 7 4,6-dichloro-2-methyl-5-pyrimidyl 1108 ″ NH S * 8 4,6-dichloro-2-methyl-5-pyrimidyl 1109 ″ NH S * 9 4,6-dichloro-2-methyl-5-pyrimidyl 1110 ″ NH S * 14 4,6-dichloro-2-methyl-5-pyrimidyl 1111 ″ O S * 1 4,6-bis(dimethylamino)-5-pyrimidyl 1112 ″ O S * 2 4,6-bis(dimethylamino)-5-pyrimidyl 1113 ″ O S * 3 4,6-bis(dimethylamino)-5-pyrimidyl 1114 ″ O S * 4 4,6-bis(dimethylamino)-5-pyrimidyl 1115 ″ O S * 5 4,6-bis(dimethylamino)-5-pyrimidyl 1116 ″ O S * 6 4,6-bis(dimethylamino)-5-pyrimidyl 1117 ″ O S * 7 4,6-bis(dimethylamino)-5-pyrimidyl 1118 ″ O S * 8 4,6-bis(dimethylamino)-5-pyrimidyl 1119 ″ O S * 9 4,6-bis(dimethylamino)-5-pyrimidyl 1120 ″ O S * 14 4,6-bis(dimethylamino)-5-pyrimidyl *Single Bond  

TABLE 57 Compound No.

X Y Z n Het 1121

S S * 1 4,6-bis(dimethylamino)-5-pyrimidyl 1122 ″ S S * 2 4,6-bis(dimethylamino)-5-pyrimidyl 1123 ″ S S * 3 4,6-bis(dimethylamino)-5-pyrimidyl 1124 ″ S S * 4 4,6-bis(dimethylamino)-5-pyrimidyl 1125 ″ S S * 5 4,6-bis(dimethylamino)-5-pyrimidyl 1126 ″ S S * 6 4,6-bis(dimethylamino)-5-pyrimidyl 1127 ″ S S * 7 4,6-bis(dimethylamino)-5-pyrimidyl 1128 ″ S S * 8 4,6-bis(dimethylamino)-5-pyrimidyl 1129 ″ S S * 9 4,6-bis(dimethylamino)-5-pyrimidyl 1130 ″ S S * 14 4,6-bis(dimethylamino)-5-pyrimidyl 1131 ″ NH S * 1 4,6-bis(dimethylamino)-5-pyrimidyl 1132 ″ NH S * 2 4,6-bis(dimethylamino)-5-pyrimidyl 1133 ″ NH S * 3 4,6-bis(dimethylamino)-5-pyrimidyl 1134 ″ NH S * 4 4,6-bis(dimethylamino)-5-pyrimidyl 1135 ″ NH S * 5 4,6-bis(dimethylamino)-5-pyrimidyl 1136 ″ NH S * 6 4,6-bis(dimethylamino)-5-pyrimidyl 1137 ″ NH S * 7 4,6-bis(dimethylamino)-5-pyrimidyl 1138 ″ NH S * 8 4,6-bis(dimethylamino)-5-pyrimidyl 1139 ″ NH S * 9 4,6-bis(dimethylamino)-5-pyrimidyl 1140 ″ NH S * 14 4,6-bis(dimethylamino)-5-pyrimidyl *Single Bond  

TABLE 58 Compound No.

X Y Z n Het 1141

O S * 1 4,6-bismethylthio-2-methyl-5-pyrimidyl 1142 ″ O S * 2 4,6-bismethylthio-2-methyl-5-pyrimidyl 1143 ″ O S * 3 4,6-bismethylthio-2-methyl-5-pyrimidyl 1144 ″ O S * 4 4,6-bismethylthio-2-methyl-5-pyrimidyl 1145 ″ O S * 5 4,6-bismethylthio-2-methyl-5-pyrimidyl 1146 ″ O S * 6 4,6-bismethylthio-2-methyl-5-pyrimidyl 1147 ″ O S * 7 4,6-bismethylthio-2-methyl-5-pyrimidyl 1148 ″ O S * 8 4,6-bismethylthio-2-methyl-5-pyrimidyl 1149 ″ O S * 9 4,6-bismethylthio-2-methyl-5-pyrimidyl 1150 ″ O S * 14 4,6-bismethylthio-2-methyl-5-pyrimidyl 1151 ″ S S * 1 4,6-bismethylthio-2-methyl-5-pyrimidyl 1152 ″ S S * 2 4,6-bismethylthio-2-methyl-5-pyrimidyl 1153 ″ S S * 3 4,6-bismethylthio-2-methyl-5-pyrimidyl 1154 ″ S S * 4 4,6-bismethylthio-2-methyl-5-pyrimidyl 1155 ″ S S * 5 4,6-bismethylthio-2-methyl-5-pyrimidyl 1156 ″ S S * 6 4,6-bismethylthio-2-methyl-5-pyrimidyl 1157 ″ S S * 7 4,6-bismethylthio-2-methyl-5-pyrimidyl 1158 ″ S S * 8 4,6-bismethylthio-2-methyl-5-pyrimidyl 1159 ″ S S * 9 4,6-bismethylthio-2-methyl-5-pyrimidyl 1160 ″ S S * 14 4,6-bismethylthio-2-methyl-5-pyrimidyl *Single Bond  

TABLE 59 Compound No.

X Y Z n Het 1161

NH S * 1 4,6-bismethylthio-2-methyl-5-pyrimidyl 1162 ″ NH S * 2 4,6-bismethylthio-2-methyl-5-pyrimidyl 1163 ″ NH S * 3 4,6-bismethylthio-2-methyl-5-pyrimidyl 1164 ″ NH S * 4 4,6-bismethylthio-2-methyl-5-pyrimidyl 1165 ″ NH S * 5 4,6-bismethylthio-2-methyl-5-pyrimidyl 1166 ″ NH S * 6 4,6-bismethylthio-2-methyl-5-pyrimidyl 1167 ″ NH S * 7 4,6-bismethylthio-2-methyl-5-pyrimidyl 1168 ″ NH S * 8 4,6-bismethylthio-2-methyl-5-pyrimidyl 1169 ″ NH S * 9 4,6-bismethylthio-2-methyl-5-pyrimidyl 1170 ″ NH S * 14 4,6-bismethylthio-2-methyl-5-pyrimidyl 1171 ″ O S * 1 2,4,6-trimethoxy-5-pyrimidyl 1172 ″ O S * 2 2,4,6-trimethoxy-5-pyrimidyl 1173 ″ O S * 3 2,4,6-trimethoxy-5-pyrimidyl 1174 ″ O S * 4 2,4,6-trimethoxy-5-pyrimidyl 1175 ″ O S * 5 2,4,6-trimethoxy-5-pyrimidyl 1176 ″ O S * 6 2,4,6-trimethoxy-5-pyrimidyl 1177 ″ O S * 7 2,4,6-trimethoxy-5-pyrimidyl 1178 ″ O S * 8 2,4,6-trimethoxy-5-pyrimidyl 1179 ″ O S * 9 2,4,6-trimethoxy-5-pyrimidyl 1180 ″ O S * 14 2,4,6-trimethoxy-5-pyrimidyl *Single Bond  

TABLE 60 Compound No.

X Y Z n Het 1181

S S * 1 2,4,6-trimethoxy-5-pyrimidyl 1182 ″ S S * 2 2,4,6-trimethoxy-5-pyrimidyl 1183 ″ S S * 3 2,4,6-trimethoxy-5-pyrimidyl 1184 ″ S S * 4 2,4,6-trimethoxy-5-pyrimidyl 1185 ″ S S * 5 2,4,6-trimethoxy-5-pyrimidyl 1186 ″ S S * 6 2,4,6-trimethoxy-5-pyrimidyl 1187 ″ S S * 7 2,4,6-trimethoxy-5-pyrimidyl 1188 ″ S S * 8 2,4,6-trimethoxy-5-pyrimidyl 1189 ″ S S * 9 2,4,6-trimethoxy-5-pyrimidyl 1190 ″ S S * 14 2,4,6-trimethoxy-5-pyrimidyl 1191 ″ NH S * 1 2,4,6-trimethoxy-5-pyrimidyl 1192 ″ NH S * 2 2,4,6-trimethoxy-5-pyrimidyl 1193 ″ NH S * 3 2,4,6-trimethoxy-5-pyrimidyl 1194 ″ NH S * 4 2,4,6-trimethoxy-5-pyrimidyl 1195 ″ NH S * 5 2,4,6-trimethoxy-5-pyrimidyl 1196 ″ NH S * 6 2,4,6-trimethoxy-5-pyrimidyl 1197 ″ NH S * 7 2,4,6-trimethoxy-5-pyrimidyl 1198 ″ NH S * 8 2,4,6-trimethoxy-5-pyrimidyl 1199 ″ NH S * 9 2,4,6-trimethoxy-5-pyrimidyl 1200 ″ NH S * 14 2,4,6-trimethoxy-5-pyrimidyl *Single Bond  

TABLE 61 Compound No.

X Y Z n Het 1201

O SO * 5 2-methylthio-3-pyridyl 1202 ″ O SO₂ * 5 2-methylthio-3-pyridyl 1203 ″ O NH * 5 2-methylthio-3-pyridyl 1204 ″ S SO * 5 2-methylthio-3-pyridyl 1205 ″ S SO₂ * 5 2-methylthio-3-pyridyl 1206 ″ S NH * 5 2-methylthio-3-pyridyl 1207 ″ NH SO * 5 2-methylthio-3-pyridyl 1208 ″ NH SO₂ * 5 2-methylthio-3-pyridyl 1209 ″ NH NH * 5 2-methylthio-3-pyridyl 1210 ″ O SO NH 6 2-methylthio-3-pyridyl 1211 ″ O SO₂ NH 6 2-methylthio-3-pyridyl 1212 ″ O NH NH 6 2-methylthio-3-pyridyl 1213 ″ S SO NH 6 2-methylthio-3-pyridyl 1214 ″ S SO₂ NH 6 2-methylthio-3-pyridyl 1215 ″ S NH NH 6 2-methylthio-3-pyridyl 1216 ″ NH SO NH 6 2-methylthio-3-pyridyl 1217 ″ NH SO₂ NH 6 2-methylthio-3-pyridyl 1218 ″ NH NH NH 6 2-methylthio-3-pyridyl *Single Bond  

TABLE 62 Compound No.

X Y Z n Het 1219

O SO * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1220 ″ O SO₂ * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1221 ″ O NH * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1222 ″ S SO * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1223 ″ S SO₂ * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1224 ″ S NH * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1225 ″ NH SO * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1226 ″ NH SO₂ * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1227 ″ NH NH * 5 2,4-bismethylthio-6-methyl-3-pyridyl 1228 ″ O SO NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1229 ″ O SO₂ NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1230 ″ O NH NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1231 ″ S SO NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1232 ″ S SO₂ NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1233 ″ S NH NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1234 ″ NH SO NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1235 ″ NH SO₂ NH 6 2,4-bismethylthio-6-methyl-3-pyridyl 1236 ″ NH NH NH 6 2,4-bismethylthio-6-methyl-3-pyridyl *Single Bond  

TABLE 63 Compound No.

X Y Z n Het 1237

O S Single Bond 5

1238

O S Single Bond 5

1239

O S Single Bond 8

1240

O S Single Bond 8

1241

O S Single Bond 5

1242

O S Single Bond 5

1243

O S Single Bond 8

1244

O S Single Bond 8

1245

S S Single Bond 1

1246

NH S Single Bond 1

 

TABLE 64 Compound No.

X Y Z n Het 1247

O S Single Bond 1

1248

O S Single Bond 2

1249

O S Single Bond 3

1250

O S Single Bond 4

1251

O S Single Bond 5

1252

O S Single Bond 6

1253

O S Single Bond 7

1254

O S Single Bond 8

1255

O S Single Bond 9

1256

O S Single Bond 14

 

TABLE 65 Compound No.

X Y Z n Het 1257

O S Single Bond 1

1258

O S Single Bond 2

1259

O S Single Bond 3

1260

O S Single Bond 4

1261

O S Single Bond 5

1262

O S Single Bond 6

1263

O S Single Bond 7

1264

O S Single Bond 8

1265

O S Single Bond 9

1266

O S Single Bond 14

 

TABLE 66 Compound No.

X Y Z n Het 1267

O S Single Bond 1

1268

O S Single Bond 2

1269

O S Single Bond 3

1270

O S Single Bond 4

1271

O S Single Bond 5

1272

O S Single Bond 6

1273

O S Single Bond 7

1274

O S Single Bond 8

1275

O S Single Bond 9

1276

O S Single Bond 14

 

TABLE 67 Compound No.

X Y Z n Het 1277

O S Single Bond 1

1278

O S Single Bond 2

1279

O S Single Bond 3

1280

O S Single Bond 4

1281

O S Single Bond 5

1282

O S Single Bond 6

1283

O S Single Bond 7

1284

O S Single Bond 8

1285

O S Single Bond 9

1286

O S Single Bond 14

 

TABLE 68 Compound No.

X Y Z n Het 1287

O S Single Bond 1

1288

O S Single Bond 2

1289

O S Single Bond 3

1290

O S Single Bond 4

1291

O S Single Bond 5

1292

O S Single Bond 6

1293

O S Single Bond 7

1294

O S Single Bond 8

1295

O S Single Bond 9

1296

O S Single Bond 14

 

TABLE 69 Compound No.

X Y Z n Het 1297

O S Single Bond 1

1298

O S Single Bond 2

1299

O S Single Bond 3

1300

O S Single Bond 4

1301

O S Single Bond 5

1302

O S Single Bond 6

1303

O S Single Bond 7

1304

O S Single Bond 8

1305

O S Single Bond 9

1306

O S Single Bond 14

 

TABLE 70 Compound No.

X Y Z n Het 1307

O S Single Bond 1

1308

O S Single Bond 2

1309

O S Single Bond 3

1310

O S Single Bond 4

1311

O S Single Bond 5

1312

O S Single Bond 6

1313

O S Single Bond 7

1314

O S Single Bond 8

1315

O S Single Bond 9

1316

O S Single Bond 14

TABLE 71 Compound No.

X Y Z n Het 1317

O S Single Bond 1

1318

O S Single Bond 2

1319

O S Single Bond 3

1320

O S Single Bond 4

1321

O S Single Bond 5

1322

O S Single Bond 6

1323

O S Single Bond 7

1324

O S Single Bond 8

1325

O S Single Bond 9

1326

O S Single Bond 14

 

TABLE 72 Compound No.

X Y Z n Het 1327

O S Single Bond 1

1328

O S Single Bond 2

1329

O S Single Bond 3

1330

O S Single Bond 4

1331

O S Single Bond 5

1332

O S Single Bond 6

1333

O S Single Bond 7

1334

O S Single Bond 8

1335

O S Single Bond 9

1336

O S Single Bond 14

 

TABLE 73 Compound No.

X Y Z n Het 1337

O S * 1 4-methyl-6-methylthio-3-pyridyl 1338 ″ O S * 2 4-methyl-6-methylthio-3-pyridyl 1339 ″ O S * 3 4-methyl-6-methylthio-3-pyridyl 1340 ″ O S * 4 4-methyl-6-methylthio-3-pyridyl 1341 ″ O S * 5 4-methyl-6-methylthio-3-pyridyl 1342 ″ O S * 6 4-methyl-6-methylthio-3-pyridyl 1343 ″ O S * 7 4-methyl-6-methylthio-3-pyridyl 1344 ″ O S * 8 4-methyl-6-methylthio-3-pyridyl 1345 ″ O S * 9 4-methyl-6-methylthio-3-pyridyl 1346 ″ O S * 14 4-methyl-6-methylthio-3-pyridyl 1347 ″ S S * 1 4-methyl-6-methylthio-3-pyridyl 1348 ″ S S * 2 4-methyl-6-methylthio-3-pyridyl 1349 ″ S S * 3 4-methyl-6-methylthio-3-pyridyl 1350 ″ S S * 4 4-methyl-6-methylthio-3-pyridyl 1351 ″ S S * 5 4-methyl-6-methylthio-3-pyridyl 1352 ″ S S * 6 4-methyl-6-methylthio-3-pyridyl 1353 ″ S S * 7 4-methyl-6-methylthio-3-pyridyl 1354 ″ S S * 8 4-methyl-6-methylthio-3-pyridyl 1355 ″ S S * 9 4-methyl-6-methylthio-3-pyridyl 1356 ″ S S * 14 4-methyl-6-methylthio-3-pyridyl * = Single Bond  

TABLE 74 Compound No.

X Y Z n Het 1357

NH S * 1 4-methyl-6-methylthio-3-pyridyl 1358 ″ NH S * 2 4-methyl-6-methylthio-3-pyridyl 1359 ″ NH S * 3 4-methyl-6-methylthio-3-pyridyl 1360 ″ NH S * 4 4-methyl-6-methylthio-3-pyridyl 1361 ″ NH S * 5 4-methyl-6-methylthio-3-pyridyl 1362 ″ NH S * 6 4-methyl-6-methylthio-3-pyridyl 1363 ″ NH S * 7 4-methyl-6-methylthio-3-pyridyl 1364 ″ NH S * 8 4-methyl-6-methylthio-3-pyridyl 1365 ″ NH S * 9 4-methyl-6-methylthio-3-pyridyl 1366 ″ NH S * 14 4-methyl-6-methylthio-3-pyridyl 1367 ″ O S * 1 5-methylthio-2-pyridyl 1368 ″ O S * 2 5-methylthio-2-pyridyl 1369 ″ O S * 3 5-methylthio-2-pyridyl 1370 ″ O S * 4 5-methylthio-2-pyridyl 1371 ″ O S * 5 5-methylthio-2-pyridyl 1372 ″ O S * 6 5-methylthio-2-pyridyl 1373 ″ O S * 7 5-methylthio-2-pyridyl 1374 ″ O S * 8 5-methylthio-2-pyridyl 1375 ″ O S * 9 5-methylthio-2-pyridyl 1376 ″ O S * 14 5-methylthio-2-pyridyl * = Single Bond  

TABLE 75 Com- pound No.

X Y Z n Het 1377

S S * 1 5-methylthio-2-pyridyl 1378 ″ S S * 2 5-methylthio-2-pyridyl 1379 ″ S S * 3 5-methylthio-2-pyridyl 1380 ″ S S * 4 5-methylthio-2-pyridyl 1381 ″ S S * 5 5-methylthio-2-pyridyl 1382 ″ S S * 6 5-methylthio-2-pyridyl 1383 ″ S S * 7 5-methylthio-2-pyridyl 1384 ″ S S * 8 5-methylthio-2-pyridyl 1385 ″ S S * 9 5-methylthio-2-pyridyl 1386 ″ S S * 14 5-methylthio-2-pyridyl 1387 ″ NH S * 1 5-methylthio-2-pyridyl 1388 ″ NH S * 2 5-methylthio-2-pyridyl 1389 ″ NH S * 3 5-methylthio-2-pyridyl 1390 ″ NH S * 4 5-methylthio-2-pyridyl 1391 ″ NH S * 5 5-methylthio-2-pyridyl 1392 ″ NH S * 6 5-methylthio-2-pyridyl 1393 ″ NH S * 7 5-methylthio-2-pyridyl 1394 ″ NH S * 8 5-methylthio-2-pyridyl 1395 ″ NH S * 9 5-methylthio-2-pyridyl 1396 ″ NH S * 14 5-methylthio-2-pyridyl * = Single Bond  

TABLE 76 Compound No.

X Y Z n Het 1397

O S * 1 2,4,6-trismethylthio-5-pyrimidyl 1398 ″ O S * 2 2,4,6-trismethylthio-5-pyrimidyl 1399 ″ O S * 3 2,4,6-trismethylthio-5-pyrimidyl 1400 ″ O S * 4 2,4,6-trismethylthio-5-pyrimidyl 1401 ″ O S * 5 2,4,6-trismethylthio-5-pyrimidyl 1402 ″ O S * 6 2,4,6-trismethylthio-5-pyrimidyl 1403 ″ O S * 7 2,4,6-trismethylthio-5-pyrimidyl 1404 ″ O S * 8 2,4,6-trismethylthio-5-pyrimidyl 1405 ″ O S * 9 2,4,6-trismethylthio-5-pyrimidyl 1406 ″ O S * 14 2,4,6-trismethylthio-5-pyrimidyl 1407 ″ S S * 1 2,4,6-trismethylthio-5-pyrimidyl 1408 ″ S S * 2 2,4,6-trismethylthio-5-pyrimidyl 1409 ″ S S * 3 2,4,6-trismethylthio-5-pyrimidyl 1410 ″ S S * 4 2,4,6-trismethylthio-5-pyrimidyl 1411 ″ S S * 5 2,4,6-trismethylthio-5-pyrimidyl 1412 ″ S S * 6 2,4,6-trismethylthio-5-pyrimidyl 1413 ″ S S * 7 2,4,6-trismethylthio-5-pyrimidyl 1414 ″ S S * 8 2,4,6-trismethylthio-5-pyrimidyl 1415 ″ S S * 9 2,4,6-trismethylthio-5-pyrimidyl 1416 ″ S S * 14 2,4,6-trismethylthio-5-pyrimidyl *Single Bond  

TABLE 77 Compound No.

X Y Z n Het 1417

NH S * 1 2,4,6-trismethylthio-5-pyrimidyl 1418 ″ NH S * 2 2,4,6-trismethylthio-5-pyrimidyl 1419 ″ NH S * 3 2,4,6-trismethylthio-5-pyrimidyl 1420 ″ NH S * 4 2,4,6-trismethylthio-5-pyrimidyl 1421 ″ NH S * 5 2,4,6-trismethylthio-5-pyrimidyl 1422 ″ NH S * 6 2,4,6-trismethylthio-5-pyrimidyl 1423 ″ NH S * 7 2,4,6-trismethylthio-5-pyrimidyl 1424 ″ NH S * 8 2,4,6-trismethylthio-5-pyrimidyl 1425 ″ NH S * 9 2,4,6-trismethylthio-5-pyrimidyl 1426 ″ NH S * 14 2,4,6-trismethylthio-5-pyrimidyl *Single Bond  

TABLE 78 Compound No.

X Y Z n Het 1427

O S Single Bond 1

1428

O S Single Bond 1

 

The compounds represented by the formula (I) in the present invention has an ACAT inhibitory activity and/or an intracellular cholesterol transfer inhibitory activity, and is useful in the medical field as medications for treating hyperlipemia or arteriosclerosis. Especially, the compounds of the present invention exhibit an activity of selectively inhibiting an ACAT enzyme which is present in the blood vessel wall. Accordingly, it is expected to have a less side effect than a non-selective ACAT inhibitor, and is preferable as an active ingredient of a drug.

The pharmaceutical composition of the present invention contains the compounds represented by the formula (I) or acid addition salts or solvates thereof as active ingredients. It comprises at least one type of the active ingredients in a therapeutically effective amount, and a pharmaceutically acceptable carrier.

The pharmaceutical composition of the present invention contains the compounds represented by the formula (I), or the acid addition salts or the solvates thereof as active ingredients. At least one type of the active ingredients is used singly, or can be shaped into an administrable preparation such as a tablet, a capsule, a granule, a powder, an injection or a suppository using a pharmaceutically acceptable carrier well-known to those skilled in the art, such as a excipient, a binder, a support or a diluent. These preparations can be produced by a known method. For example, an orally administrable preparation can be produced by mixing the compound represented by the formula (I) with an excipient such as starch, mannitol or lactose, a binder such as carboxymethylcellulose sodium or hydroxypropyl cellulose, a disintegrant such as crystalline cellulose or carboxymethyl cellulose calcium, a lubricant such as talc or magnesium stearate, and a fluidity improving agent such as light silicic anhydride, which are combined as required.

The pharmaceutical composition of the present invention can be administered either orally or parenterally.

The dose of the pharmaceutical composition of the present invention varies depending on the weight, the age, the sex, the progression of disease and the like of patients. Generally, it is preferably administered to an adult person at a dose of from 1 to 100 mg, preferably from 5 to 200 mg a day, from one to three times a day.

The ACAT inhibitory activity of the compounds represented by the formula (I) in the present invention was tested in the following Experiment Examples.

Experiment Example 1

(ACAT Inhibitory Activity)

A microsome was prepared from the breast aorta of a rabbit which had been fed with 1% cholesterol food for 8 weeks in a usual manner, and suspended in a 0.15 M phosphate buffer solution (pH 7.4) to form an enzyme solution. An enzyme solution derived from the small intestine was prepared from the small intestine of a rabbit that had eaten a normal food.

The ACAT inhibitory activity was measured by modifying the method of J. G. Heider (J. Lipid Res., 24, 1127-1134, 1983). That is, 2 μl of a test compound dissolved in dimethyl sulfoxide (DMSO) were added to 88 μl of a 0.15 M phosphate buffer solution (pH 7.4)containing ¹⁴C-Oleoyl-CoA (40 μM, 60,000 dpm) and bovine serum albumin (2.4 mg/ml), and the mixture was incubated at 37° C. for 5 minutes.

To this solution were added 10 μl of the enzyme solution, and the mixture was reacted at 37° C. for 5 minutes (for 3 minutes in the case of the small intestine). Then, 3 ml of a chloroform/methanol (2/1) mixture and 0.5 ml of 0.04 N hydrochloric acid were added thereto to stop the reaction. The lipid was then extracted. The solvent layer was concentrated to dryness, and dissolved in hexane. The solution was spotted on a TLC plate (supplied by Merck Co.). The elution was conducted with a hexane:ether:acetic acid (75:25:1) mixture.

The radioactivity of the resulting cholesterol ester fraction was measured using BAS 2000 (supplied by Fuji Photo Film Co., Ltd.). An IC₅₀ value was obtained from the calculation in contrast with a control containing only DMSO. The results are shown in Table 79.

TABLE 79 Test Compound Enzyme from A* Enzyme from B* IC₅₀ (B*)/ No. IC₅₀ (μM) IC₅₀ (μM) IC₅₀ (A*) 795 0.028 0.016 0.6 811 0.014 0.38 27.1 815 0.014 0.017 1.2 818 0.0056 0.016 2.9 831 0.63 0.61 1.0 Control 1 0.43 0.87 1.9 Control 2 0.047 0.13 2.8 Control 3 0.034 0.056 1.7 Control 4 0.026 0.037 1.4 Control 5 0.01 0.065 6.5 Control 6 0.11 0.51 4.6 A*: the blood vessel wall B*: the small intestine  

Experiment Example 2

(ACAT Inhibitory Activity (Anti-foamation Activity) in J744 Cells and HepG2 Cells)

J774 cells or HepG2 cells were spread on a 24-well plate. The cells were incubated in a 5% CO₂ incubator at 37° C. for 24 hours using DMEM in the case of the J774 cells and a MEM culture solution in the case of the HepG2 cells (both containing 10% fetal calf serum).

The medium was replaced with 0.5 ml of each culture solution containing 10 μg/ml of 25-OH cholesterol and a test piece, and the cells were further incubated for 18 hours.

The medium was removed, and the residue was washed twice with PBS, then extracted with 1.5 ml of a hexane:isopropanol (3:2) mixture, and concentrated to dryness. The extract was dissolved in 0.2 ml of isopropanol containing 10% Triton X-100. Total cholesterol (TC) and free cholesterol (FC) were measured using Cholesterol E Test Wako (supplied by Wako Pure Chemical Industries, Ltd.) and Free Cholesterol E Test Wako (supplied by Wako Pure Chemical Industries, Ltd.).

The cell extract residue was solubilized in 0.25 ml of 2N NaOH at 37° C. for 30 minutes, and the protein amount was measured using BCA Protein Assay Reagent (Pierce).

The amount of cholesterol based on the protein was calculated from the difference between TC and FC, and an IC₅₀ value was obtained from the calculation in contrast with the control results are shown in Table 80.

TABLE 80 Test Compound Enzyme (1774) Enzyme (HepG2) IC₅₀ (HepG2)/ No. IC₅₀ (μM) IC₅₀ (μM) IC₅₀ (1774)  795 0.050 0.35 7.0  797 0.0036 0.029 8.1  811 0.050 1.8 36.0  815 0.12 2.6 21.7  818 0.062 0.063 1.0  831 0.057 5.4 94.7 1253 0.0041 0.0044 1.1 1282 0.0032 0.0062 1.9 1292 0.0027 0.030 11.1 1294 0.0042 0.0024 0.6 1302 0.0021 0.015 7.1 Control 1 0.56 5.3 9.5 Control 2 0.58 1.1 1.9 Control 3 0.32 1.3 4.3 Control 4 0.12 0.75 6.3 Control 5 1.9 1.6 0.8 Control 6 0.28 9.1 32.8  

As control compounds, the following control compounds (1) to (6) were subjected to the same test, and the results are also shown in Tables 64 and 65. Control Compounds (1) to (6) are as follows.

Control compound (1):

5-[2-(2-(4-fluorophenyl)ethyl)-3-(1-methyl-1H-imidazol-2-yl)-2H-1-benzopyran-6-yl]oxy-2,2-dimethyl-N-(2,6-diisopropylphenyl)pentanamide (WO 92/09582)

Control compound (2):

(+)-(S)-2-[5-(3,5-dimethylpyrazol-1-yl)pentasulfinyl]-4,5-diphenylimidazole (EP 523941)

Control compound (3):

N-(2,2,5,5-tetramethyl-1,3-dioxan-4-ylcarbonyl)-β-alanine 2 (S)-[N′-(2,2-dimethylpropyl)-N′-nonylureido]-1(S)-cyclohexyl ester (EP 421441)

Control compound (4):

[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-N-heptyl-2-benzoxazolamie (WO 93/23392)

Control compound (5):

6-(benzoxazol-2-ylthio)-N-(2,6-diisopropylphenyl)hexanamide (compound of Japanese Patent Application No. 88,660/1997)

Control compound (6):

2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-(2,6-diisopropylphenyl)acetamide (compound of Japanese Patent Application No. 149,892/1997)

EXAMPLES

The present invention is illustrated more specifically by referring to the following Examples. However, the present invention is not limited to these Examples.

Example 1 (Compound No. 5 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-(2-methylthio-3-pyridyl)hexanamide:

A methanol (50 ml) solution of 2-chloro-3-nitropyridine (4.30 g, 27.1 mmol) was added dropwise to a methanol (30 ml) solution of sodium thiomethoxide (2.10 g, 28.5 mmol) while being cooled with ice, and the mixed solution was stirred for 17 hours. Water was then added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crystals were recrystallized from a mixture of an ethyl acetate-hexane mixture to obtain 2.93 g (yield 64%) of 2-methylthio-3-nitropyridine as a yellow needle crystal.

This nitropyridine (851 mg, 5.0 mmol) was dissolved in a mixed solvent of acetic acid (35 ml) and conc. hydrochloric acid (1.4 ml), and zinc (3.92 g, 60 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 30 minutes, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 600 mg (yield 86%) of 3-amino-2-methylthiopyridine as a pale yellow oil.

Triethylamine (520 mg, 5.14 mmol) was added to a THF (7 ml) solution of this aminopyridine (600 mg, 4.28 mmol). Subsequently, 6-bromohexanoyl chloride (1.10 g, 5.14 mmol) was slowly added dropwise thereto while being cooled with ice, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 125 g, eluent-hexane:ethyl acetate=6:1→3:1→2:1) to obtain 1.08 g (yield 79%) of 6-bromo-N-(2-methylthio-3-pyridyl)hexanamide as a colorless needle crystal (melting point: 66 to 67° C.).

To a DMF (2 ml) solution of this amide (159 mg, 0.5 mmol) and 2-mercaptobenzoxazole (83 mg, 0.55 mmol) were added 18-crown-6 (13 mg, 0.05 mmol) and potassium carbonate (83 mg, 0.6 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography silica gel 20 g, eluent-hexane:ethyl acetate=5:2→2:1) to obtain 156 g (yield 81%) of a desired compound as a colorless needle crystal.

Melting point: 127-128° C.

IR (KBr) cm⁻¹: 3447, 3265, 1654, 1522, 1508.

¹H-NMR (CDCl₃) δ: 1.58-1.65 (2H, m), 1.83 (2H, quint, J=7.4 Hz), 1.92 (2H, quint, J=7.4 Hz), 2.46 (2H, t, J=7.4 Hz), 2.62 (3H, s), 3.34 (2H, t, J=7.4 Hz), 7.06 (1H, dd, J=8.1, 4.6 Hz), 7.21-7.30 (3H, m), 7.44 (1H, m), 7.59 (1H, m), 8.26 (1H, d, J=4.6 Hz), 8.28 (1H, d, J=8.1 Hz).

EIMS m/z (relative intensity): 387 (M⁺), 165 (100).

Elemental analysis: as C₁₉H₂₁N₃O₂S₂; calculated: C, 58.89; H, 5.46; N, 10.84; S, 16.55. found: C, 58.92; H, 5.43; N, 10.78; S, 16.55.

Example 2 (Compound No. 8 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-(2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 9-bromononanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain 9-bromo-N-(2-methylthio-3-pyridyl)nonanamide.

To a DMF (5 ml) solution of this amide (90 mg, 0.25 mmol) and 2-mercaptobenzoxazole (38 mg, 0.25 mmol) were added potassium carbonate (42 mg, 0.30 mmol) and 18-crown-6 (7 mg, 0.03 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was allowed to cool, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting residue was recrystallized from a mixture of ethyl acetate-hexane to obtain 83 mg (yield 77%) of the desired compound as a colorless powdery crystal.

Melting point: 84-85° C.

IR (KBr) cm⁻¹: 3465, 3276, 2926, 1664, 1505.

¹H-NMR (CDCl₃) δ: 1.35-1.53 (8H, m), 1.72-1.77 (2H, m), 1.80-1.87 (2H, m), 2.42 (2H, t, J=7.3 Hz). 2.63 (3H, s), 3.31 (2H, t, J=7.4 Hz), 7.06 (1H, dd, J=8.0, 4.7 Hz), 7.21-7.30 (3H, m), 7.43 (1H, dd, J=7.0, 0.6 Hz), 7.59 (1H, dd, J=7.6, 0.6 Hz), 8.25 (1H, d, J=4.7 Hz), 8.31 (1H, d, J=7.8 Hz).

EIMS m/z (relative intensity): 429 (M⁺), 297 (100).

Elemental analysis: as C₂₂H₂₇N₃O₂S₂; calculated: C, 61.51; H, 6.33; N, 9.78; S, 14.93. found: C, 61.51; H, 6.28; N, 9.64; S, 14.99.

Example 3 (Compound No. 15 in Table)

Production of 6-(benzothiazol-2-ylthio)-N-(2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 118-119° C.

IR (KBr) cm⁻¹: 3429, 3265, 1654, 1522, 1508.

¹H-NMR (CDCl₃) δ: 1.57-1.65 (2H, m), 1.83 (2H, quint, J=7.4 Hz), 1.91 (2H, quint, J=7.4 Hz), 2.46 (2H, t, J=7.4 Hz), 2.61 (3H, s), 3.38 (2H, t, J=7.4 Hz), 7.06 (1H, dd, J=8.1, 4.9 Hz), 7.25 (1H, br s), 7.29 (1H, m), 7.41 (1H, m), 7.75 (1H, m), 7.86 (1H, m), 8.25 (1H, d, J=4.9 Hz), 8.29 (1H, d, J=8.1 Hz).

EIMS m/z (relative intensity): 403 (M⁺), 223 (100).

Elemental analysis: as C₁₈H₂₁N₃OS₃; calculated: C, 56.55; H, 5.24N, 10.41; S, 23.83. found: C, 56.69; H, 5.30; N, 10.24; S, 23.77.

Example 4 (Compound No. 18 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-(2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 2 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 107-108° C.

IR (KBr) cm⁻¹: 3448, 3256, 2923, 1656, 1525.

¹H-NMR (d6-DMSO) δ: 1.24-1.34 (6H, m), 1,36-1.43 (2H, m), 1.54-1.59 (2H, m), 1.69-1.77 (2H, m), 2.26 (2H, t, J=7.4 Hz), 2.40 (3H, s), 3.28 (2H, t, J=7.2 Hz), 7.01 (1H, dd, J=7.8, 4.6 Hz), 7.26 (1H, dt, J=8.1, 1.2 Hz), 7.36 (1H, dt, J=7.3, 1.2 Hz), 7.58 (1H, dd, J=7.8, 1.5 Hz), 7.74 (1H, d, J=8.1 Hz), 7.85 (1H, dd, J=7.3, 1.2 Hz), 8.21 (1H, dd, J=4.6, 1.5 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 445 (M⁺), 297 (100).

Elemental analysis: as C₂₂H₂₇N₃OS₃; calculated: C, 59.29; H, 6.11; N, 9.43; S, 21.58. found: C, 59.12; H, 6.02; N, 9.25; S, 21.62.

Example 5 (Compound No. 25 in Table)

Production of 6-(benzimidazol-2-ylthio)-N-(2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow needle crystal.

Melting point: 121-123° C.

IR (KBr) cm⁻¹: 3386, 3276, 1658, 1511, 1398.

¹H-NMR (CDCl₃) δ: 1.52-1.60 (2H, m), 1.74-1.86 (4H, m), 2.42 (2H, t, J=7.2 Hz), 2.60 (3H, s), 3.32 (2H, t, J=7.2 Hz), 7.05 (1H, dd, J=8.1, 4.9 Hz), 7.18-7.19 (2H, m), 7.32 (1H, br s), 7.36 (1H, br s), 7.66 (1H, br s), 8.23-8.26 (2H, m), 9.84 (1H, br s).

EIMS m/z (relative intensity): 386 (M⁺), 205 (100).

Elemental analysis: as C₁₉H₂₂N₄OS₂; calculated: C, 59.04; H, 5.74; N, 14.49; S, 16.59. found: C, 59.06; H, 5.76; N, 14.35; S, 16.57.

Example 6 (Compound No. 28 in Table)

Production of 9-(benzimidazol-2-ylthio)-N-(2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 2 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

IR (KBr) cm⁻¹: 3260, 2929, 2851, 1664, 1519, 1394.

¹H-NMR (CDCl₃) δ: 1.31-1.47 (6H, m), 1.57-1.61 (2H, m), 1.69-1.79 (4H, m), 2.42 (2H, t, J=7.2 Hz), 2.63 (3H, s), 3.32 (2H, t, J=7.4 Hz), 7.06 (1H, dd, J=8.1, 4.6 Hz), 7.18-7.23 (4H, m), 7.67 (1H, br s), 8.26 (1H, d, J=4.6 Hz), 8.30 (1H, d, J=7.8 Hz), 9.31 (1H, br s).

EIMS m/z (relative intensity): 428 (M⁺), 164 (100).

Example 7 (Compound No. 158 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-(4-methyl-2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 2-chloro-4-methyl-3-nitropyridine was used instead of 2-chloro-3-nitropyridine to obtain 4-methyl-2-methylthio-3-nitropyridine. This nitropyridine (474 mg, 2.57 mmol) was dissolved in a mixed solvent of acetic acid (18 ml) and conc. hydrochloric acid (0.7 ml), and zinc (2.02 g, 30.88 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 30 minutes, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 307 mg (yield 77%) of 3-amino-4-methyl-2-methylthiopyridine as a colorless crystal.

Triethylamine (302 mg, 2.99 mmol) was added to a chloroform (4 ml) solution of this aminopyridine (307 mg, 1.99 mmol), and a chloroform (4 ml) solution of 9-bromononanyl chloride (2.99 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 125 g, eluent-hexane:ethyl acetate=3:1→2:1) to obtain 261 mg (yield 35%) of 9-bromo-N-(4-methyl-2-methylthio-3-pyridyl)nonanamide as a colorless powdery crystal (melting point: 77 to 78° C.). To a DMF (5 ml) solution of this amide (114 mg, 0.31 mmol) and 2-mercaptobenzoxazole (46 mg, 0.31 mmol) were added 18-crown-6 (8 mg, 0.03 mmol) and potassium carbonate (51 mg, 0.37 mmol), and the mixture was stirred at 80° C. for 2 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through preparative thin-layer chromatography (eluent-chloroform:methanol=20:1) to obtain 89 mg (yield 66%) of the desired compound as a colorless powdery crystal.

Melting point 91-92° C.

IR (KBr) cm⁻¹: 3433, 3268, 2924, 1518, 1496. ¹H-NMR (CDCl₃) δ: 1.36-1.53 (8H, m), 1.74-1.88 (4H, m), 2.21 (3H, s), 2.43 (2H, t, J=7.6 Hz), 2.53 (3H, s), 3.32 (2H, t, J=7.3 Hz), 6.63 (1H, br s), 6.90 (1H, d, J=5.1 Hz), 7.22-7.30 (1H, m), 7.43 (1H, dd, J=7.2, 1.4 Hz), 7.60 (1H, dd, J=7.6, 1.4 Hz), 8.24 (1H, d, J=4.9 Hz).

EIMS m/z (relative intensity); 443 (M⁺, 100).

Elemental analysis: as C₂₃H₂₉N₃O₂S₂; calculated: C, 62.27; H, 6.59; N, 9.47; S, 14.45. found: C, 62.34; H, 6.58; N, 9.33; S, 14.44.

Example 8 (Compound No. 168 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-(4-methyl-2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 7 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 88-90° C.

IR (KBr) cm⁻¹: 3449, 3271, 2925, 1657, 1425, 997.

¹H-NMR (CDCl₃) δ: 1.37-1.53 (8H, m), 1.73-1.87 (4H, m), 2.21 (3H, s), 2.43 (2H, t, J=7.6 Hz), 2.53 (3H, s), 3.35 (2H, t, J=7.3 Hz), 6.62 (1H, br s), 6.90 (1H, d, J=5.1 Hz), 7.23-7.31 (1H, m), 7.39-7.43 (1H, m), 7.75 (1H, dd, J=8.1, 0.5 Hz), 7.86 (1H, dd, J=8.1, 0.5 Hz), 8.24 (1H, d, J=5.1 Hz).

Elemental analysis: as C₂₃H₂₉N₃OS₃; calculated: C, 60.10; H, 6.36N, 9.14. found: C, 59.99; H, 6.36; N, 9.00.

Example 9 (Compound No. 275 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-[2,6-bis(methylthio)-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 2,6-dichloro-3-nitropyridine was used instead of 2-chloro-3-nitropyridine. This nitropyridine (800 mg, 3.70 mmol) was dissolved in a mixed solvent of acetic acid (100 ml) and conc. hydrochloric acid (5.6 ml), and zinc (2.90 g, 44.39 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 30 minutes, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent:hexane:ethyl acetate=4:1) to obtain 301 mg (yield 44%) of 3-amino-2,6-bis(methylthio)pyridine as a pale yellow powdery crystal.

Triethylamine (196 mg, 1.94 mmol) was added to a THF (3 ml) solution of this aminopyridine (301 mg, 1.62 mmol), and a THF (1 ml) solution of 6-bromohexanoyl chloride (345 mg, 1.62 mmol) was then slowly added thereto dropwise while being cooled with ice, and the mixture was stirred at 0° C. for 3 hours. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate=4:1) to obtain 453 mg (yield 77%) of 6-bromo-N-[2,6-bis(methylthio)-3-pyridyl]hexanamide as a colorless powdery crystal (melting point: 117 to 119° C.). To a DMF (4 ml) solution of this amide (100 mg, 0.28 mmol) and 2-mercaptobenzoxazole (42 mg, 0.28 mmol) were added 18-crown-6 (7 mg, 0.03 mmol) and potassium carbonate (46 mg, 0.33 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was recrystallized from a mixture of ethyl acetate and hexane to obtain 83 mg (yield 70%) of the desired compound as a colorless powdery crystal.

Melting point: 125-126° C.

IR (KBr) cm⁻¹: 3436, 3253, 2937, 1653, 1519, 1505.

¹H-NMR (CDCl₃) δ: 1.57-1.65 (2H, m), 1.78-1.86 (2H, m), 1.88-1.95 (2H, m), 2.44 (2H, t, J=7.4 Hz), 2.57 (3H, s), 2.62 (3H, s), 3.33 (2H, t, J=7.3 Hz), 6.93 (1H, d, J=8.4 Hz), 7.02 (1H, br s), 7.21-7.30 (2H, m), 7.43 (1H, dd, J=7.4, 1.7 Hz), 7.59 (1H, dd, J=7.4, 1.7 Hz), 8.01 (1H, d, J=8.4 Hz),

Elemental analysis: as C₂₀H₂₃N₃O₂S₃; calculated: C, 55.40; H, 5.35; N, 9.69. found: C, 55.53; H, 5.38; N, 9.68.

Example 10 (Compound No. 455 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 1 except that 2-chloro-6-methyl-3-nitropyridine was used instead of 2-chloro-3-nitropyridine to obtain 6-methyl-2-methylthio-3-nitropyridine. This nitropyridine (921 mg, 5.0 mmol) was dissolved in a mixed solvent of acetic acid (40 ml) and conc. hydrochloric acid (1.75 ml), and zinc (3.81 g, 60 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 30 minutes, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 685 mg (yield 88%) of 3-amino-6-methyl-2-methylthiopyridine as a yellow oil.

Triethylamine (475 mg, 4.7 mmol) was added to a chloroform (10 ml) solution of this aminopyridine (601 mg, 3.9 mmol), and 6-bromohexanoyl chloride (944 mg, 4.29 mmol) was then slowly added thereto dropwise while being cooled with ice, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with water, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 50 g, eluent-hexane:ethyl acetate=10:1→5:1) to obtain 773 mg (yield 59%) of 6-bromo-N-(6-methyl-2-methylthio-3-pyridyl)hexanamide as a colorless crystal (melting point: 98 to 99° C.). To a DMF (2 ml) solution of this amide (133 mg, 0.4 mmol) and 2-mercaptobenzoxazole (67 mg, 0.44 mmol) were added 18-crown-6 (11 mg, 0.04 mmol) and potassium carbonate (67 mg, 0.44 mmol), and the mixture was stirred at 80° C. for 90 minutes. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 20 g, eluent-hexane:acetone=5:1→5:3) to obtain 125 mg (yield 78%) of the desired compound as a colorless needle crystal.

Melting point: 140-141° C.

IR (KBr) cm⁻¹: 3437, 3267, 1654, 1528, 1506.

¹H-NMR (CDCl₃) δ: 1.57-1.65 (2H, m), 1.82 (2H, quint, J=7.4 Hz), 1.91 (2H, quint, J=7.4 Hz), 2.44 (2H, t, J=7.4 Hz), 2.48 (3H, s), 2.60 (3H, s), 3.33 (2H, t, J=7.4 Hz), 6.90 (1H, d, J=8.1 Hz), 7.21-7.30 (2H, m), 7.43 (1H, m), 7.59 (1H, m), 8.13 (1H, d, J=8.1 Hz).

EIMS m/z (relative intensity): 401 (M⁺), 203 (100).

Elemental analysis: as C₂₀H₂₃N₃O₂S₂; calculated: C, 59.82; H, 5.77; N, 10.46. found: C, 59.90; H, 5.84; N, 10.32.

Example 11 (Compound No. 458 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)nonanamide:

Triethylamine (607 mg, 6.0 mmol) was added to a chloroform (10 ml) solution of 3-amino-6-methyl-2-methylthiopyridine (685 mg, 4.44 mmol), and a chloroform (3 ml) solution of 9-bromononanyl chloride (1,281 mg, 5 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 75 g, eluent-hexane:ethyl acetate=10:1→4:1) to obtain 433 mg (yield 27%) of 9-bromo-N-(6-methyl-2-methylthio-3-pyridyl)nonanamide as a colorless crystal (melting point: 80 to 82° C.).

To a DMF (1.5 ml) solution of this amide (131 mg, 0.35 mmol) and 2-mercaptobenzoxazole (58 mg, 0.385 mmol) were added 18-crown-6 (9 mg, 0.035 mmol) and potassium carbonate (58 mg, 0.42 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 30 g, eluent-hexane:ethyl acetate=4:1→3:1) to obtain 123 mg (yield 79%) of the desired compound as a colorless needle crystal.

Melting point: 99-100° C.

IR (KBr) cm⁻¹: 3421, 3235, 2924, 1655, 1528, 1497, 1455.

¹H-NMR (CDCl₃) δ: 1.32-1.42 (6H, m), 1.43-1.51 (2H, m), 1.70-1.78 (2H, m), 1.83 (2H, quint, J=7.4 Hz), 2.40 (2H, t, J=7.4 Hz), 2.48 (3H, s), 2.61 (3H, s), 3.31 (2H, t, J=7.4 Hz), 6.90 (1H, d, J=8.1 Hz), 7.21-7.30 (3H, m), 7.43 (1H, m), 7.60 (1H, m), 8.15 (1H, d, J=8.1 Hz).

EIMS m/z (relative intensity): 443 (M⁺), 311 (100).

Example 12 (Compound No. 465 in Table)

Production of 6-(benzothiazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 10 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 122-123° C.

IR (KBr) cm⁻¹: 3438, 3290, 1656, 1515, 1431.

¹H-NMR (CDCl₃) δ: 1.57-1.65 (2H, m), 1.82 (2H, quint, J=7.4 Hz), 1.90 (2H, quint, J=7.4 Hz), 2.44 (2H, t, J=7.4 Hz), 2.48 (3H, s), 2.60 (3H, s), 3.37 (2H, t, J=7.4 Hz), 6.90 (1H, d, J=8.3 Hz), 7.22(1H, br s) 7.29 (1H, m), 7.41 (1H, m), 7.75 (1H, m), 7.86 (1H, m), 8.13 (1H, J=8.3 Hz).

EIMS m/z (relative intensity): 417 (M⁺), 168 (100).

Elemental analysis: as C₂₀H₂₃N₃OS₃; calculated: C, 57.52; H, 5.55; N, 10.06. found: C, 57.65; H, 5.63; N, 9.97.

Example 13 (Compound No. 468 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 11 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 104-105° C.

IR (KBr) cm⁻¹: 3280, 2924, 1662, 1527, 1428.

¹H-NMR (CDCl₃) δ: 1.32-1.41 (6H, m), 1.43-1.51 (2H, m), 1.70-1.77 (2H, m), 1.82 (2H, quint, J=7.4 Hz), 2.40 (2H, t, J=7.4 Hz), 2.48 (3H, s), 2.61 (3H, s), 3.34 (2H, t, J=7.4 Hz), 6.90 (1H, d, J=8.1 Hz), 7.22 (1H, br s) 7.29 (1H, m), 7.41 (1H, m), 7.76 (1H, m), 7.86 (1H, m), 8.15 (1H, d, J=8.1 Hz),

EIMS m/z (relative intensity): 459 (M⁺), 293 (100).

Elemental analysis: as C₂₃H₂₉N₃OS₃; calculated: C, 60.10; H, 6.36; N, 9.14. found: C, 60.17; H, 6.40; N, 9.11.

Example 14 (Compound No. 475 in Table)

Production of 6-(benzimidazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 10 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 138-140° C.

IR (KBr) cm⁻¹: 3385, 3244, 1668, 1509, 1440.

¹H-NMR (CDCl₃) δ: 1.53-1.61 (2H, m), 1.78 (2H, quint, J=7.6 Hz), 1.82 (2H, quint, J=7.6 Hz), 2.41 (2H, t, J=7.6 Hz), 2.48 (3H, s), 2.59 (3H, s), 3.31 (2H, t, J=7.6 Hz), 6.88 (1H, d, J=8.3 Hz), 7.16-7.23 (2H, m), 7.31-7.32 (2H, m), 7.67 (1H, m), 8.08 (1H, d, J=8.3 Hz), 9.72 (1H, br s).

EIMS m/z (relative intensity): 400 (M⁺), 164 (100).

Elemental analysis: as C₂₀H₂₄N₄OS₂; calculated: C, 59.97; H, 6.04; N, 13.99. found: C, 60.08; H, 6.08; N, 13.94.

Example 15 (Compound No. 478 in Table)

Production of 9-(benzimidazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 11 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 73-75° C.

IR (KBr) cm⁻¹: 3254, 2926, 1663, 1515, 1438.

¹H-NMR (CDCl₃) δ: 1.27-1.43 (8H, m), 1.68-1.78 (4H, m), 2.40 (2H, t, J=7.4 Hz), 2.48 (3H, s), 2.60 (3H, s), 3.31 (2H, t, J=7.4 Hz), 6.89 (1H, d, J=8.1 Hz), 7.17-7.20 (2H, m), 7.31-7.33 (2H, m), 7.67 (1H, m), 8.13 (1H, d, J=8.1 Hz), 9.69 (1H, br s).

Example 16 (Compound No. 781 in Table)

Production of 2-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide:

Triethylamine (274 mg, 2.71 mmol) was added to a chloroform (10 ml) solution of 3-amino-2,4-bis(methylthio)-6-methylpyridine (492 mg, 2.46 mmol), and bromoacetyl bromide (521 mg, 2.58 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and then extracted with methylene chloride. The organic layer was washed with 1N hydrochloric acid, water, an aqueous solution of sodium hydrogencarbonate, water and a saturated aqueous solution of sodium chloride in this order, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 25 g, eluent-hexane:acetone=7:1→5:1→3:1) to obtain 100 mg (yield 13%) of 2-bromo-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide as a colorless crystal (melting point: 171 to 172° C.).

Potassium carbonate (46 mg, 0.33 mmol) was added to an acetonitrile (5 ml) solution of this amide (96 mg, 0.3 mmol) and 2-mercaptobenzoxazole (45 mg, 0.3 mmol), and the mixture was stirred at room temperature for 90 minutes. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 10 g, eluent-hexane:acetone=5:2) to obtain 88 mg (yield 75%) of the desired compound as a colorless crystal.

Melting point: 203-205° C.

IR (KBr) cm⁻¹: 3437, 3238, 1669, 1509, 1454.

¹H-NMR (CDCl₃) δ: 2.31 (3H, s), 2.41 (3H, s), 2.46 (3H, s), 4.10 (2H, s), 6.61 (1H, s), 7.28-7.33 (2H, m), 7.49 (1H, m), 7.60 (1H, m), 8.77 (1H, br s).

EIMS m/z (relative intensity): 391 (M⁺), 227 (100).

Elemental analysis: as C₁₇H₁₇N₃O₂S₃; calculated: C, 52.15; H, 4.38; N, 10.73. found: C, 52.14; H, 4.44; N, 10.57.

Example 17 (Compound No. 783 in Table)

Production of 4-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]butanamide:

Triethylamine (206 mg, 2.04 mmol) was added to a THF (6 ml) solution of 3-amino-2,4-bis(methylthio)-6-methylpyridine (341 mg, 1.70 mmol), and 4-bromobutanoyl chloride (379 mg, 2.04 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 75 g, eluent-hexane:acetone=5:1→3:1) to obtain 390 mg (yield 66%) of 4-bromo-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]butanamide as a colorless crystal (melting point: 139 to 140° C.).

To a DMF (2 ml) solution of this amide (105 mg, 0.3 mmol) and 2-mercaptobenzoxazole (50 mg, 0.33 mmol) were added 18-crown-6 (8 mg, 0.03 mmol) and potassium carbonate (50 mg, 0.36 mmol), and the mixture was stirred at 80° C. for 3 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through preparative thin-layer chromatography (eluent-hexane:ethyl acetate=3:2, eluted twice) to obtain 67 mg (yield 53%) of the desired compound as a colorless needle crystal.

Melting point: 149-150° C.

IR (KBr) cm⁻¹: 3437, 3248, 1667, 1503, 1455.

¹H-NMR (d6-DMSO) δ: 2.13 (2H, quint, J=7.2 Hz), 2.37 (3H, s), 2.38 (3H, s), 2.44 (3H, s), 2.49 (2H, t, J=7.2 Hz), 3.43 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.30-7.37 (2H, m), 7.64-7.68 (2H, m), 9.45 (1H, br s).

EIMS m/z (relative intensity): 419 (M⁺, 100).

Elemental analysis: as C₁₉H₂₁N₃O₂S₃; calculated: C, 54.39; H, 5.04; N, 10.01. found: C, 54.58; H, 5.08; N, 9.98.

Example 18 (Compound No. 785 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 6-bromohexanoyl chloride was used instead of 4-bromobutanoyl chloride to obtain the desired compound as a colorless powdery crystal.

Melting point: 120-121° C.

IR (KBr) cm⁻¹: 3433, 3235, 1662, 1502, 1455.

¹H-NMR (d6-DMSO) δ: 1.44-1.54 (2H, m), 1.58-1.68 (2H, m), 1.72-1.82 (2H, m), 2.18-2.27 (2H, m), 2.32 (3H, s), 2.34 (3H, s), 2.37 (3H, s), 3.27 (2H, t, J=7.2 Hz), 6.78 (1H, s), 7.19-7.26 (2H, m), 7.47-7.53 (2H, m), 8.74 (1H, br s).

EIMS m/z (relative intensity): 446 (M⁺−1), 200 (100).

Elemental analysis: as C₂₁H₂₅N₃O₂S₃; calculated: C, 56.35; H, 5.63; N, 9.39; S, 21.49. found: C, 56.42; H, 5.62; N, 9.26; S, 21.39.

Example 19 (Compound No. 788 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 9-bromononanoyl chloride was used instead of 4-bromobutanoyl chloride to obtain the desired compound as a colorless powdery crystal.

Melting point; 123-124° C.

IR (KBr) cm⁻¹: 3461, 3246, 1671, 1504, 1454.

¹H-NMR (d6-DMSO) δ: 1.26-1.46 (8H, m), 1.53-1.63 (2H, m), 1.72-1.83 (2H, m), 2.24 (2H, t, J=7.3 Hz), 2.37 (3H, s), 2.38 (3H, s), 2.43 (3H, s), 3.31-3.41 (2H, m), 6.86 (1H, s), 7.27-7.34 (2H, m), 7.58-7.66 (2H, m), 9.26 (1H, br s).

EIMS m/z (relative intensity): 489 (M⁺, 100).

Elemental analysis: as C₂₄H₃₁N₃O₂S₃; calculated: C, 58.86; H, 6.38; N, 8.58; S, 19.64. found: C, 58.94; H, 6.37; N, 8.44, S, 19.55.

Example 20 (Compound No. 793 in Table)

Production of 4-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 131-133° C.

IR (KBr) cm⁻¹: 3435, 3250, 1665, 1509, 1428.

¹H-NMR (d6-DMSO) δ: 2.11 (2H, quint, J=7.2 Hz), 2.37 (3H, s), 2.38 (3H, s), 2.44 (3H, s), 2.49 (2H, t, J=7.2 Hz), 3.46 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.37 (1H, m), 7.47 (1H, m), 7.87 (1H, m), 8.02 (1H, m), 9.45 (1H, s).

EIMS m/z (relative intensity): 435 (M⁺), 168 (100).

Elemental analysis: as C₁₉H₂₁N₃OS₄; calculated: C, 52.39; H, 4.86; N, 9.65. found: C, 52.39; H, 4.84; N, 9.56.

Example 21 (Compound No. 795 in Table)

Production of 6-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 18 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow crystal.

Melting point: 123-125° C.

IR (KBr) cm⁻¹: 3433, 3258, 2923, 1661, 1429.

¹H-NMR (d6-DMSO) δ: 1.49-1.58 (6H, m), 1.67 (2H, quint, J=7.2 Hz), 1.83 (2H, quint, J=7.2 Hz), 2.29 (2H, t, J=7.2 Hz), 2.38 (3H, s), 2.39 (3H, s), 2.45 (3H, s), 3.38 (2H, t, J=7.2 Hz), 6.68 (1H, s), 7.36 (1H, td, J=8.0, 1.0 Hz), 7.46 (1H, td, J=8.0, 1.0 Hz), 7.86 (1H, dd, J=8.0, 1.0 Hz), 8.01 (1H, br d, J=8.0 Hz), 9.31 (1H, s).

EIMS m/z (relative intensity): 463 (M⁺), 201 (100).

Elemental analysis: as C₂₁H₂₅N₃OS₄; calculated: C, 54.40; H, 5.43; N, 9.06; S, 27.66. found: C, 54.42, H, 5.45; N, 8.79; S, 27.68.

Example 22 (Compound No. 798 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 19 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 126-127° C.

IR (KBr) cm⁻¹: 3440, 3252, 2924, 1661, 1430.

¹H-NMR (d6-DMSO) δ: 1.31-1.52 (8H, m), 1.59-1.68 (2H, m), 1.77-1.85 (2H, m), 2.23-2.33 (2H, m), 2.40 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 3.36 (2H, t, J=7.2 Hz), 6.86 (1H, s), 7.34 (1H, dt, J=7.8, 1.2 Hz), 7.44 (1H, dt, J=7.8, 1.2 Hz), 7.83 (1H, d, J=8.3 Hz). 7.93 (1H, dt, J=7.8, 0.6 Hz), 8.78 (1H, br s).

EIMS m/z (relative intensity): 504 (M+−1), 200 (100).

Elemental analysis: as C₂₄H₃₁N₃OS₄; calculated: C, 57.00; H, 6.18; N, 8.31; S, 25.36. found: C, 57.08; H, 6.17; N, 8.15; S, 25.41.

Example 23 (Compound No. 803 in Table)

Production of 4-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow needle crystal.

Melting point: 177-179° C.

IR (KBr) cm⁻¹: 3421, 3147, 1659, 1645, 1438.

¹H-NMR (d6-DMSO) δ: 2.06 (2H, quint, J=7.2 Hz), 2.38 (3H, s), 2.39 (3H, s), 2.44 (3H, s), 2.46 (2H, t, J=7.2 Hz), 3.36 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.09-7.13 (2H, m), 7.34-7.52 (2H, m), 9.48 (1H, s), 12.54 (1H, br s).

EIMS m/z (relative intensity): 418 (M⁺), 150 (100).

Example 24 (Compound No. 805 in Table)

Production of 6-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 18 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 139-141° C.

IR (KBr) cm⁻¹: 3433, 3244, 2924, 1659, 1437.

¹H-NMR (d6-DMSO) δ: 1.47-1.56 (2H, m), 1.65 (2H, quint, J=7.2 Hz), 1.76 (2H, quint, J=7.2 Hz), 2.28 (2H, t, J=7.2 Hz), 2.38 (3H, s), 2.39 (3H, s), 2.44 (3H, s), 3.29 (2H, t, J=7.2 Hz), 6.68 (1H, s), 7.08-7.13 (2H, m), 7.36 (1H, m), 7.50 (1H, m), 9.30 (1H, s), 12.50 (1H, br s).

EIMS m/z (relative intensity): 446 (M⁺), 200 (100).

Example 25 (Compound No. 808 in Table)

Production of 9-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 19 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

IR (KBr) cm⁻¹: 3146, 2925, 2854, 1660, 1523, 1437.

¹H-NMR (d6-DMSO) δ: 1.25-1.44 (8H, m), 1.53-1.61 (2H, m), 1.65-1.74 (2H, m), 2.24 (2H, t, J=7.3 Hz), 2.37 (3H, s), 2.38 (3H, s), 2.43 (3H, s), 3.26 (2H, t, J=7.1 Hz), 6.86 (1H, s), 7.07-7.12 (2H, m), 7.32-7.37 (1H, m), 7.46-7.54 (1H, m), 9.26 (1H, s).

EIMS m/z (relative intensity): 488 (M⁺), 150 (100).

Example 26 (Compound No. 811 in Table)

Production of 2-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

Ethanethiol (1.55 g, 25 mmol) was added dropwise to an ethanol (50 ml) solution of sodium ethoxide (1.27 g, 25 mmol) while being cooled with ice, and the mixture was stirred for 30 minutes. While being cooled with ice, a DMF (40 ml) solution of 2,4-dichloro-6-methyl-3-nitropyridine (2.1 g, 10 mmol) was slowly added thereto dropwise. After the mixture was stirred for 2 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 2.45 g (yield 95%) of 2,4-bis(ethylthio)-6-methyl-3-nitropyridine as a yellow needle crystal.

This nitropyridine (775 mg, 3 mmol) was dissolved in a mixed solvent of acetic acid (30 ml) and conc. hydrochloric acid (1.5 ml), and zinc (4 g, 60 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 10 minutes, the reaction mixture was filtered, and the filtrate was neutralized with a sodium hydroxide aqueous solution, and extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 590 mg (yield 86%) of 3-amino-2,6-bis(ethylthio)-6-methylpyridine as a yellow oil. Triethylamine (304 mg, 3 mmol) was added to a THF (10 ml) solution of this aminopyridine (590 mg, 2.6 mmol), and bromoacetyl bromide (606 mg, 3 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated. Then, the residue was purified through silica gel chromatography (silica gel 60 g, eluent-hexane:acetone=10:1→5:1) to obtain 410 mg (yield 45%) of 2-bromo-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide as a light brown needle crystal. Potassium carbonate (46 mg, 0.33 mmol) was added to an acetonitrile (3 ml) solution of this amide (105 mg, 0.3 mmol) and 2-mercaptobenzoxazole (45 mg, 0.3 mmol), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through preparative thin-layer chromatography (eluent-hexane:ethyl acetate=3:1) to obtain 70 mg (yield 56%) of the desired compound as a colorless needle crystal.

Melting point: 143-145° C.

IR (KBr) cm⁻¹: 3429, 3224, 1673, 1509, 1454.

¹H-NMR (CDCl₃) δ: 1.17 (3H, t, J=7.3 Hz), 1.20 (3H, t, J=7.5 Hz), 2.43 (3H, s), 2.81 (2H, q, J=7.3 Hz), 3.04 (2H, q, J=7.5 Hz), 4.11 (2H, s), 6.63 (1H, s), 7.25-7.33 (2H, m), 7.48 (1H, m), 7.61 (1H, m), 8.63 (1H, br s).

EIMS m/z (relative intensity): 419 (M⁺), 268 (100).

Elemental analysis: as C₁₉H₂₁N₃O₂S₃; calculated: C, 54.39; H, 5.04; N, 10.01. found: C, 54.39; H, 5.05; N, 10.00.

Example 27 (Compound No. 815 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 26 except that 6-bromohexanoyl chloride was used instead of bromoacetyl bromide to obtain 6-bromo-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]hexanamide. To a DMF (2 ml) solution of this amide (122 mg, 0.3 mmol) and 2-mercaptobenzoxazole (45 mg, 0.3 mmol) were added potassium carbonate (46 mg, 0.33 mmol) and 18-crown-6 (8 mg, 0.03 mmol), and the mixture was stirred at 80° C. for 1.5 hours. The reaction mixture was allowed to cool, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting residue was purified through preparative thin-layer chromatography (eluent-hexane:acetone=5:2) to obtain 65 mg (yield 46%) of the desired compound as a light brown needle crystal.

Melting point: 100-103° C.

IR (KBr) cm⁻¹: 3233, 2928, 1668, 1504, 1455.

¹H-NMR (d6-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.58 (2H, m), 1.70 (2H, m), 1.85 (2H, m), 2.32 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz), 3.35 (2H, t, J=7.3 Hz), 6.89 (1H, s), 7.26-7.34 (2H, m), 7.54-7.62 (2H, m), 8.77 (1H, br s).

EIMS m/z (relative intensity); 475 (M⁺, 100).

Elemental analysis: as C₂₃H₂₉N₃O₂S₃; calculated: C, 58.08; H, 6.14; N, 8.83; S, 20.22. found: C, 58.07; H, 6.13; N, 8.66; S, 20.27.

Example 28 (Compound No. 818 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 9-bromononanoyl chloride was used instead of 6-bromohexanoyl bromide to obtain the desired compound as a colorless needle crystal.

Melting point: 84-87° C.

IR (KBr) cm⁻¹: 3252, 2923, 1665, 1501, 1455.

¹H-NMR (d6-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.28-1.52 (8H, m), 1.63 (2H, m), 1.82 (2H, quint, J=7.2 Hz), 2.26 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz), 3.34 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.26-7.34 (2H, m), 7.54-7.62 (2H, m), 8.72 (1H, br s).

EIMS m/z (relative intensity): 517 (M⁺), 367 (100).

Elemental analysis: as C₂₆H₃₅N₃O₂S₃; calculated: C, 60.31; H, 6.81; N, 8.12. found: C, 60.52; H, 6.85; N, 7.85.

Example 29 (Compound No. 821 in Table)

Production of 2-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide;

The reaction and the treatment were conducted in the same manner as in Example 26 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 119-120° C.

IR (KBr) cm⁻¹: 3453, 3254, 1672, 1510, 1428.

¹H-NMR (CDCl₃) δ: 1.20 (3H, t, J=7.4 Hz), 1.22 (3H, t, J=7.4 Hz), 2.42 (3H, s), 2.82 (2H, q, J=7.4 Hz), 3.06 (2H, q, J=7.4 Hz), 4.18 (2H, s), 6.63 (1H, s), 7.33 (1H, m), 7.42 (1H, m), 7.77 (1H, m), 7.91 (1H, m), 8.95 (1H, br s).

EIMS m/z (relative intensity): 435 (M⁺), 148 (100).

Elemental analysis: as C₁₉H₂₁N₃OS₄; calculated: C, 52.39; H, 4.86; N, 9.65. found: C, 52.40; H, 4.86; N, 9.53.

Example 30 (Compound No. 825 in Table)

Production of 6-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 81-83° C.

IR (KBr) cm⁻¹: 3150, 2927, 1647, 1524, 1428.

¹H-NMR (d6-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.57 (2H, m), 1.69 (2H, m), 1.84 (2H, m), 2.29 (2H, m), 2.42 (3H, s), 2.93 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.36 (2H, t, J=7.3 Hz), 6.87 (1H, s), 7.33 (1H, m), 7.43 (1H, m), 7.82 (1H, m), 7.92 (1H, m), 8.77 (1H, br s).

EIMS m/z (relative intensity): 491 (M⁺), 168 (100).

Elemental analysis: as C₂₃H₂₉N₃OS₄; calculated: C, 56.18; H, 5.94; N, 8.55; S, 26.08. found: C, 56.19; H, 5.91; N, 8.43; S, 26.06.

Example 31 (Compound No. 828 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 28 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 88-92° C.

IR (KBr) cm⁻¹: 3433, 3241, 2928, 1668, 1510.

¹H-NMR (d6-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.28-1.54 (8H, m), 1.62 (2H, m), 1.80 (2H, quint, J=7.2 Hz), 2.24 (2H, m), 2.42 (3H, s), 2.93 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.35 (2H, t, J=7.2 Hz), 6.87 (1H, s), 7.33 (1H, m), 7.43 (1H, m), 7.81 (1H, m), 7.92 (1H, m), 8.72 (1H, br s).

Example 32 (Compound No. 831 in Table)

Production of 2-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 26 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 182-183° C.

IR (KBr) cm⁻¹: 3148, 2928, 1674, 1524, 1412.

¹H-NMR (d6-DMSO) δ: 1.21 (3H, t, J=7.3 Hz), 1.21 (3H, t, J=7.3 Hz), 2.41 (3H, s), 2.90 (2H, q, J=7.3 Hz), 3.03 (2H, q, J=7.3 Hz), 4.15 (2H, br s), 6.87 (1H, s), 7.08-7.12 (2H, m), 7.39-7.44 (2H, m).

EIMS m/z (relative intensity): 418 (M⁺), 357 (100).

Elemental analysis: as C₁₉H₂₂N₄OS₃; calculated: C, 54.52; H, 5.30; N, 13.38. found: C, 54.44; H, 5.30; N, 13.16.

Example 33 Compound No. 835 in Table)

Production of 6-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 139-142° C.

IR (KBr) cm⁻¹: 3433, 3143, 2928, 1660, 1510.

¹H-NMR (CDCl₃) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.54 (2H, m), 1.68 (2H, m), 1.77 (2H, m), 2.28 (2H, m), 2.42 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.27 (2H, t, J=7.2 Hz), 6.87 (1H, s), 7.05-7.11 (2H, m), 7.27-7.52 (2H, m), 8.75 (1H, br s), 12.05 (1H, br s).

Example 34 (Compound No. 838 in Table)

Production of 9-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 28 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 76-78° C.

IR (KBr) cm⁻¹: 3104, 2928, 2854, 1658, 1526.

¹H-NMR (d6-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.28-1.49 (8H, m), 1.61 (2H, m), 1.73 (2H, quint, J=7.2 Hz), 2.24 (2H, m), 2.42 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.26 (2H, t, J=7.2 Hz), 6.87 (1H, s), 7.05-7.10 (2H, m), 7.24-7.54 (2H, m), 8.71 (1H, br s), 12.05 (1H, br s).

Example 35 (Compound No. 841 in Table)

Production of 2-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

To a 2-propanol (50 ml) solution of sodium isopropoxide (2.05 g, 25 mmol) was added dropwise 2-propanethiol (1.90, 25 mmol) while being cooled with ice, and the mixtrue was stirred for 30 minutes. While being cooled with ice, a DMF (40 ml) solution of 2,4-dichloro-6-methyl-3-nitropyridine (2.07 g, 10 mmol) was slowly added thereto dropwise. After the mixture was stirred for 2 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off to obtain 2.77 g (yield 97%) of 2,4-bis(isopropylthio)-6-methyl-3-nitropyridine as a yellow needle crystal.

This nitropyridine (1.08 g, 3.77 mmol) was dissolved in a mixed solvent of acetic acid (35 ml) and conc. hydrochloric acid (1.6 ml), and zinc (2.96 g, 45.25 mmol) was added thereto in small portions while being cooled with ice. After the mixture was stirred for 1 hour, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with chloroform. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting residue was purified through silica gel column chromatography (eluent-hexane:ethyl acetate=30:1→10:1) to obtain 774 mg (yield 80%) of 3-amino-2,4-bis(isopropylthio)-6-methylpyridine as a yellow oil. Triethylamine (336 mg, 3.32 mmol) was added to a THF (10 ml) solution of this aminopyridine (774 mg, 3.02 mmol), and bromoacetyl bromide (732 mg, 3.62 mmol) was then slowly added thereto dropwise while being cooled with ice, and the mixture was stirred for 17 hours. The reaction mixture was filtered, and the filtrate was concentrated. Then, the residue was purified through silica gel chromatography (eluent-hexane:ethyl acetate=10:1) to obtain 595 mg (yield 52%) of 2-bromo-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide as a colorless powdery crystal, sodium hydrogencarbonate (29 mg, 0.35 mmol) was added to an acetonitrile (5 ml) solution of this amide (132 mg, 0.35 mmol) and 2-mercaptobenzoxazole (53 mg, 0.35 mmol), and the mixture was stirred at room temperature for 28 hours. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through preparative thin-layer chromatography (eluent-hexane:benzen=6:1) to obtain 69 mg (yield 44%) of the desired compound as a colorless powdery crystal.

Melting point: 151-152° C.

IR (KBr) cm⁻¹: 3404, 2967, 1743, 1637, 1360.

¹H-NMR (CDCl₃) δ: 1.37-1.40 (12H, m), 2.52 (3H, s), 3.58 (1H, sept, J=6.8 Hz), 4.06 (2H, s), 4.11 (1H, sept, J=6.8 Hz), 6.01 (1H, s). 6.81-6.86 (2H, m), 6.92 (1H, dd, J=8.1, 1.3 Hz), 7.00-7.07 (2H, m).

Example 36 (Compound No. 845 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 35 except that 6-bromohexanoyl chloride was used instead of bromoacetyl bromide to obtain 6-bromo-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide. To a DMF (4 ml) solution of this amide (100 mg, 0.23 mmol) and 2-mercaptobenzoxazole (35 mg, 0.23 mmol) were added potassium carbonate (38 mg, 0.28 mmol) and 18-crown-6 (6 mg, 0.02 mmol), and the mixture was stirred at 80° C. for 2.5 hours. The reaction mixture was allowed to cool, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting residue was purified through preparative thin-layer chromatography (eluent-hexane:ethyl acetate=3:1) to obtain 92 mg (yield 79%) of the desired compound as a colorless powdery crystal.

Melting point: 98-100° C.

IR (KBr) cm⁻¹: 3135, 2961, 1648, 1498, 1454, 1133.

¹H-NMR (d6-DMSO) δ: 1.32 (6H, d, J=6.8 Hz), 1.35 (6H, d, J=6.8 Hz), 1.55-1.64 (2H, m), 1.65-1.75 (2H, m), 1.82-1.92 (2H, m), 2.23-2.36 (2H, m), 2.46 (3H, s), 3.38 (2H, t, J=7.1 Hz), 3.59 (1H, sept, J=6.8 Hz), 3.93 (1H, sept, J=6.8 Hz), 6.96 (1H, s), 7.29-7.37 (2H, m), 7.57-7.64 (2H, m), 8.95 (1H, br s).

Example 37 (Compound No. 1237 in Table)

Production of 6-(oxazolo[4,5-b]pyridin-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide:

To a DMF (4 ml) solution of 6-bromo-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide (100 mg, 0.27 mmol) and 2-mercaptoxazolo[4,5-b]pyridine (40 mg, 0.27 mmol) were added 18-crown-6 (7 mg, 0.03 mmol) and potassium carbonate (40 mg, 0.29 mmol), and the mixture was stirred at 80° C. for 4 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through preparative thin-layer chromatography (eluent-hexane:acetone=2:1) to obtain 85 mg (yield 72%) of the desired compound as a colorless powdery crystal.

Melting point: 132-133° C.

IR (KBr) cm⁻¹: 3435, 3243, 2923, 1655, 1493, 1404.

¹H-NMR (d6-DMSO) δ: 1.53-1.63 (2H, m), 1.65-1.76 (2H, m), 1.83-1.93 (2H, m), 2.27-2.35 (2H, m), 2.40 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 3.40 (2H, t, J=7.3 Hz), 6.86 (1H, s), 7.30 (1H, dd, J=8.1, 4.9 Hz), 7.97 (1H, dd, J=8.1, 1.3 HZ), 8.42 (1H, dd, J=4.9, 1.3 HZ), 8.83 (1H, br s).

EIMS m/z (relative intensity): 447 (M⁺−1), 400 (100).

Elemental analysis: as C₂₀H₂₄N₄O₂S₃; calculated: C, 53.55; H, 5.39; N, 12.59; S, 21.44. found: C, 53.72; H, 5.39; N, 12.41; S, 21.51.

Example 38 (Compound No. 1238 in Table)

Production of 6-(7-methoxycarbonylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 37 except that 7-methoxycarbonyl-2-mercaptobenzoxazole was used instead of 2-mercaptoxazolo[4,5-b]pyridine to obtain the desired compound as a colorless powdery crystal.

Melting point: 141-142° C.

IR (KBr) cm⁻¹: 3425, 3236, 2923, 1726, 1667, 1509.

¹H-NMR (d6-DMSO) δ: 1.54-1.63 (2H, m), 1.67-1.76 (2H, m), 1.84-1.93 (2H, m), 2.28-2.35 (2H, m), 2.40 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 3.39 (2H, t, J=7.1 Hz), 3.95 (3H, s), 6.86 (1H, s), 7.44 (1H, t, J=7.8 Hz), 7.81 (1H, dd, J=7.8, 1.2 Hz), 7.85 (1H, dd, J=7.8, 1.2 Hz), 8.82 (1H, br s).

EIMS m/z (relative intensity): 504 (M⁺−1), 167 (100).

Elemental analysis: as C₂₃H₂₇N₃O₄S₃; calculated: C, 54.63; H, 5.38; N, 8.31; S, 19.02. found: C, 54.70; H, 5.37; N, 8.27; S, 19.15.

Example 39 (Compound No. 1240 in Table)

Production of 9-(7-methoxycarbonylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]nonanamide:

To a DMF (4 ml) solution of 9-bromo-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]nonanamide (90 mg, 0.22 mmol) and 7-methoxycarbonyl-2-mercaptobenzoxazole (45 mg, 0.22 mmol) were added 18-crown-6 (6 mg, 0.02 mmol) and potassium carbonate (36 mg, 0.26 mmol), and the mixture was stirred at 80° C. for 4 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was recrystallized from a mixture of ethyl acetate and hexane to obtain 84 mg (yield 72%) of the desired compound as a colorless powdery crystal.

Melting point: 126-128° C.

IR (KBr) cm⁻¹: 3231, 2924, 1720, 1657, 1508, 1297.

¹H-NMR (d6-DMSO) δ: 1.27-1.47 (8H, m), 1.54-1.62 (2H, m), 1.74-1.85 (2H, m), 2.24 (2H, t, J=7.3 Hz), 2.37 (3H, s), 2.38 (3H, s), 2.43 (3H, s), 3.31-3.41 (2H, m), 3.91 (3H, s), 6.86 (1H, s), 7.45 (1H, t, J=7.8 Hz), 7.81 (1H, dd, J=7.8, 1.0 Hz), 7.91 (1H, dd, J=7.8, 1.0 Hz), 9.26 (1H, s).

EIMS m/z (relative intensity), 546 (M⁺−1), 500 (100).

Elemental analysis: as C₂₆H₃₃N₃O₄S₃; calculated: C, 57.01; H, 6.07; N, 7.67; S, 17.56. found: C, 57.10; H, 5.95; N, 7.67; S, 17.60.

Examples 40 (Compound No. 151 in Table)

Production of 2-(benzoxazol-2-ylthio)-N-(4-methyl-2-methylthio-3-pyridyl)acetamide:

The reaction and the treatment were conducted in the same manner as in Example 16 except that 3-amino-4-methyl-2-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless needle crystal.

Melting point: 146-148° C.

IR (KBr) cm⁻¹: 3437, 3245, 1671, 1659, 1507, 1454.

¹H-NMR (CDCl₃) δ: 2.17 (3H, s), 2.42 (3H, s), 4.11 (2H, s), 6.87 (1H, d, J=4.9 Hz), 7.28-7.34 (2H, m), 7.50 (1H, m), 7.61 (1H, m), 8.23 (1H, d, J=4.9 Hz), 8.88 (1H, br s).

EIMS m/z (relative intensity): 345 (M⁺, 100).

Elemental analysis: as C₁₆H₁₅N₃O₂S₃; calculated: C, 55.63; H, 4.38; N, 12.16; S, 18.56. found: C, 55.66; H, 4.46, N, 12.02; S, 18.55.

Example 41 (Compound No. 155 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-(4-methyl-2-methylthio-3-pyridyl)hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 18 except that 3-amino-4-methyl-2-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless needle crystal.

Melting point: 122-124° C.

IR (KBr) cm⁻¹: 3437, 3245, 1660, 1521, 1507, 1133.

¹-NMR (d₆-DMSO) δ: 1.49-1.56 (2H, m), 1.68 (2H, quint, J=7.4 Hz), 1.84 (2H, quint, J=7.4 Hz), 2.09 (3H, s), 2.33 (2H, t, J=7.4 Hz), 2.40 (3H, s), 3.36 (2H, t, J=7.4 Hz), 7.02 (1H, d, J=4.9 Hz), 7.29-7.36 (2H, m), 7.61-7.66 (2H, m), 8.24 (1H, d, J=4.9 Hz), 9.40 (1H, br s).

EIMS m/z (relative intensity): 401 (M⁺, 100).

Elemental analysis: as C₂₀H₂₃N₃O₂S₂; calculated: C, 59.82; H, 5.77; N, 10.46; S, 15.97. found: C, 59.93; H, 5.89; N, 10.34; S, 15.99.

Example 42 (Compound No. 365 in Table)

Production of 6-(benzoxasole-2-ylthio)-N-(6-methoxy-2-methylthio-3-pyridyl)hexanamide:

A methanol (100 ml) solution of 2-chloro-6-methoxy-3-nitropyridine (2.0 g, 10.4 mmol) was added dropwise to a methanol (20 ml) solution of sodium thiomethoxide (805 mg, 10.9 mmol) while being cooled with ice, and the temperature thereof was raised to the room temperature and the mixed solution was stirred for 17 hours and the precipitated crystal was filtered to obtain 1.26 g (yield 59%) of 6-methoxy-2-methylthio-3-nitropyridine as a yellow powdery crystal.

This nitropyridine (400 mg, 2.0 mmol) was dissolved in a mixed solvent of acetic acid (20 ml) and conc. hydrochloric acid (0.5 ml), and zinc (1.57 g, 24.0 mmol) was added thereto in small portions while being cooled with ice for 5 minutes. After the mixture was stirred for 40 minutes at the room temperature, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate=6:1→4:1) to obtain 264 mg (yield 78%) of 3-amino-6-methoxy-2-methylthiopyridine as a pale brown powdery crystal.

And then the reaction and the treatment were conducted in the same manner as in Example 18 except that 3-amino-6-methoxy-2-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

Melting point: 102-104° C.

IR (KBr) cm⁻¹: 3430, 3224, 2940, 1652, 1591.

¹H-NMR (CDCl₃) δ: 1.61 (2H, quint, J=7.4 Hz), 1.82 (2H, quint, J=7.4 Hz). 1.92 (2H, quint, J=7.4 Hz), 2.42 (2H, t, J=7.4 Hz), 2.59 (3H, s), 3.34 (2H, t, J=7.4 Hz), 3.94 (3H, s), 6.47 (1H, d, J=8.5 Hz), 6.91 (1H, br s), 7.23 (1H, td, J=7.7, 1.5 Hz), 7.27 (1H, td, J=7.7, 1.5 Hz), 7.43 (1H, dd, J=7.7, 1.5 Hz), 7.58 (1H, dd, J=7.7, 1.5 Hz), 7.93 (1H, d, J=8.5 Hz).

EIMS m/z (relative intensity): 417 (M⁺), 171 (100).

Example 43 (Compound No. 451 in Table)

Production of 2-(benzoxazol-2-ylthio)-N-(6-methylthio-3-pyridyl)acetamide:

The reaction and the treatment were conducted in the same manner as in Example 16 except that 3-amino-6-methyl-2-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless needle crystal.

Melting point: 180-181° C.

IR (KBr) cm⁻¹: 3437, 3254, 1661, 1534, 1509, 1135.

¹H-NMR (CDCl₃) δ: 2.46 (3H, s), 2.50 (3H, s), 4.10 (2H, s), 6.87 (2H, d, J=8.1 Hz), 7.26-7.34 (2H, m), 7.48 (1H, m), 7.62 (1H, m), 8.12 (2H, d, J=8.1 Hz), 9.27 (1H, br s).

EIMS m/z (relative intensity): 345 (M⁺), 298 (100).

Elemental analysis: as C₁₆H₁₅N₃O₂S₂; calculated: C, 55.63; H, 4.38; N, 12.16; S, 18.56. found: C, 55.62; H, 4.40; N, 12.10; S, 18.50.

Example 44 (Compound No. 461 in Table)

Production of 2-(benzothiazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)acetamide:

The reaction and the treatment were conducted in the same manner as in Example 43 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting Point: 175-176° C.

IR (KBr) cm⁻¹: 3437, 3248, 1656, 1532, 1430.

¹H-NMR (CDCl₃) δ: 2.45 (3H, s), 2.47 (3H, s), 4.18 (2H, s), 6.87 (1H, d, J=8.1 Hz), 7.34 (1H, m), 7.44 (1H, m), 7.77 (1H, m), 8,01 (1H, m), 8.07 (1H, d, J=8.1 Hz), 9.31 (1H, br s).

EIMS m/z (relative intensity): 361 (M⁺), 210 (100).

Elemental analysis: as C₁₆H₁₅N₃OS₂; calculated: C, 53.16; H, 4.18; N, 11.62; S, 26.61. found: C, 53.23; H, 4.25; N, 11.55; S, 26.67.

Example 45 (Compound No. 471 in Table)

Production of 2-(benzimidazol-2-ylthio)-N-(6-methyl-2-methylthio-3-pyridyl)acetamide:

The reaction and the treatment were conducted in the same manner as in Example 43 except that 2-2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 192-193° C. (d.)

IR (KBr) cm⁻¹: 3420, 3249, 1667, 1550, 1438, 744.

¹H-NMR (CDCl₃) δ: 2.45 (3H, s), 2.50 (3H, s), 4.08 (2H, s), 6.84 (1H, d, J=8.1 Hz), 7.19-7.25 (2H, m), 7.35 (1H, m), 7.73 (1H, m), 8.00 (1H, d, J=8.1 Hz), 9.95 (1H, br s), 10.00 (1H, br s).

EIMS m/z (relative intensity): 344 (M⁺), 118 (100).

Elemental analysis: as C₁₆H₁₆N₄OS₂; calculated: C, 55.79; H, 4.68; N, 16.27; S, 18.62. found: C, 55.80; H, 4.68; N, 16.16; S, 18.65.

Example 46 (Compound No. 784 in Table)

Production of 5-(benzoxazol-2-ylthio)-N-(2,4-bis(methylthio)-6-methyl-3-pyridyl)pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 5-bromopentanoic acid chloride was used instead of 4-bromobutanoyl chloride to obtain the desired compound as a colorless needles crystal.

Melting point: 147-150° C.

IR (KBr) cm⁻¹: 3230, 1664, 1501, 1455, 1136.

¹H-NMR (d₆-DMSO) δ: 1.72-1.96 (4H, m), 2.36 (3H, s), 2.26-2.42 (2H, m), 2.39 (3H, s), 2.43 (3H, s), 3.36 (2H, t, J=7.2 Hz), 6.83 (1H, s), 7.23-7.33 (2H, m), 7.52-7.59 (2H, m), 8.74 (1H, br s).

EIMS m/z (relative intensity): 433 (M⁺), 201 (100).

Example 47 (Compound No. 786 in Table)

Production of 7-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 7-bromoheptanonyl chloride was used instead of 4-bromobutanoyl chloride to obtain the desired compound as a colorless powdery crystal.

Melting point: 137-139° C.

IR (KBr) cm⁻¹: 3437, 3242, 2922, 2857, 1660, 1500, 1455, 1132.

¹H-NMR (d₆-DMSO) δ: 1.41-1.54 (4H, m), 1.60-1.70 (2H, m), 1.81 (2H, quint, J=7.1 Hz), 2.26-2.32 (2H, m), 2.38 (3H, s), 2.40 (3H, s), 2.43 (3H, s), 3.33 (2H, t, J=7.1 Hz), 6.81 (1H, s), 7.27 (1H, td, J=7.6, 1.7 Hz), 7.30 (1H, td, J=7.6, 1.7 Hz), 7.54-7.60 (2H, m), 8.79 (1H, br s).

EIMS m/z (relative intensity): 461 (M⁺), 200 (100).

Example 48 (Compound No. 787 in Table)

Production of 8-(benzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 17 except that 8-bromooctanoyl chloride was used instead of 4-bromobutanonyl chloride to obtain the desired compound as a colorless prism crystal.

Melting point: 119-122° C.

IR (KBr) cm⁻¹: 3435, 3248, 2923, 2856, 1660, 1501, 1454, 1131.

¹H-NMR (d₆-DMSO) δ: 1.33-1.52 (6H, m), 1.58-1.69 (2H, m), 1.81 (2H, quint, J=7.1 Hz), 2.26-2.32 (2H, m), 2.38 (3H, s), 2.41 (3H, s), 2.44 (3H, s), 3.33 (2H, t, J=7.1 Hz), 6.84 (1H, s), 7.27 (1H, td, J=7.6, 1.7 Hz), 7.30 (1H, td, J=7.6, 1.7 Hz), 7.54-7.60 (2H, m), 8.77 (1H, br s).

EIMS m/z (relative intensity): 475 (M⁺), 200 (100).

Example 49 (Compound No. 791 in Table)

Production of 2-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl)acetamide:

An acetonitrile solution (6 ml) of 2-bromo-N-[2,4-bis(methylthio)-3-pyridyl]acetamide (64 mg, 0.2 mmol) was added to an acetonitrile solution (1 ml) of sodium hydrogencarbonate (17 mg, 0.2 mmol) and 2-mercaptobenzothiazole (34 mg, 0.2 mmol), and the mixed solution was stirred for 48 hours at the room temperature. And the solution of reaction mixture was concentrated under reduced pressure, and the residue was extraxted with ethyl acetate after dilluting with water. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through preparative thin layer chromatography (eluent-chloroform:methanol=20:1) to obtain 46 mg (yield 33%) as a colorless needle crystal.

Melting point: 178-179° C.

IR (KBr) cm⁻¹: 3437, 3246, 1665, 1564, 1497, 1430.

¹H-NMR (CDCl₃) δ: 2.33 (3H, s), 2.44 (3H, s), 2.46 (3H, s), 4.17 (2H, s), 6.61 (1H, s), 7.33 (1H, m), 7.43 (1H, m), 7.78 (1H, m), 7.90 (1H, m), 9.11 (1H, br s).

EIMS m/z (relative intensity): 407 (M⁺), 209 (100).

Elemental analysis: as C₁₇H₁₇N₃OS₄; calculated: C, 50.10; H, 4.20; N, 10.31; S, 31.46. found: C, 50.18; H, 4.29; N, 10.23; S, 31.49.

Example 50 (Compound No. 794 in Table)

Production of 5-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl)pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 46 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 121-123° C.

IR (KBr) cm⁻¹: 3437, 3240, 2923, 1664, 1515, 1456, 1428, 995.

¹H-NMR (d₆-DMSO) δ: 1.78-1.87 (2H, m), 1.88-1.96 (2H, m), 2.30-2.40 (2H, m), 2.38 (3H, s), 2.41 (3H, s), 2.45 (3H, s), 3.41 (2H, t, J=7.1 Hz), 6.85 (1H, s), 7.34 (1H, t, J=7.6 Hz), 7.45 (1H, t, J=7.6 Hz), 7.84 (1H, d, J=7.6 Hz), 7.94 (1H, d, J=7.6 Hz), 8.87 (1H, br s).

EIMS m/z (relative intensity): 449 (M⁺), 201 (100).

Example 51 Compound No. 796 in Table

Production of 7-(benzothiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl)heptamamide:

The reaction and the treatment were conducted in the same manner as in Example 47 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 129-130° C.

IR (KBr) cm⁻¹: 3436, 3245, 2922, 1661, 1506, 1428.

¹H-NMR (d₆-DMSO) δ: 1.44-1.54 (4H, m), 1.62-1.71 (2H, m), 1.83 (2H, quint, J=7.2 Hz), 2.13-2.33 (2H, m), 2.39 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 3.37 (2H, t, J=7.2 Hz), 6.86 (1H, s), 7.34 (1H, td, J=7.8, 1.2 Hz), 7.45 (1H, td, J=7.8, 1.2 Hz), 7.84 (1H, dd, J=7.8, 1.2 Hz), 7.94 (1H, dd, J=7.8, 1.2 Hz), 8.81 (1H, br s).

EIMS m/z (relative intensity): 477 (M⁺), 200 (100).

Elemental analysis: as C₂₂H₂₇N₃OS₄; calculated: C, 55.31; H, 5.70; N, 8.80. found: C, 55.41; H, 5.71; N, 8.64.

Example 52 Compound No. 797 in Table

Production of 8-(benzthiazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl)octanamide:

The reaction and the treatment were conducted in the same manner as in Example 48 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 104-108° C.

IR (KBr) cm⁻¹: 3242, 2925, 1665, 1508, 1459, 1428.

¹H-NMR (d₆-DMSO) δ: 1.30-1.51 (6H, m), 1.55-1.69 (2H, m), 1.81 (2H, quint, J=7.1 Hz), 2.23-2.29 (2H, m), 2.38 (3H, s), 2.41 (3H, s), 2.44 (3H, s), 3.35 (2H, t, J=7.2 Hz), 6.83 (1H, s), 7.32 (1H, m), 7.43 (1H, m), 7.81 (1H, m), 7.91 (1H, m), 8.76 (1H, br s).

EIMS m/z (relative intensity): 491 (M⁺), 200 (100).

Example 53 Compound No. 801 in Table

Production of 2-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl)pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 49 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenothiazole to obtain the desired compound as a colorless needle crystal.

Melting point: 235-237° C. (d.)

IR (KBr) cm⁻¹: 3429, 3243, 2978, 2923, 1661, 1505, 1439.

¹H-NMR (CDCl₃) δ: 2.35 (3H, s), 2.46 (3H, s), 2.47 (3H, s), 4.03 (2H, s), 6.63 (1H, s), 7.21 (1H, t, J=6.1 Hz), 7.22 (1H, t, J=6.1 Hz), 7.43-7.60 (2H, m), 9.43 (1H, br s).

EIMS m/z (relative intensity): 390 (M⁺), 344 (100).

Example 54 Compound No. 804 in Table

Production of 5-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 46 except that 2-mercaptobenzimdazole was used instead of 2-mercaptobenoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 176-177° C.

¹H-NMR (d₆-DMSO) δ: 1.74-1.84 (4H, m), 2.26-2.35 (2H, m), 2.36 (3H, s), 2.39 (3H, s), 2.43 (3H, s), 3.26-3.36 (2H, m), 6.84 (1H, s), 7.04-7.13 (2H, m), 7.34-7.45 (2H, m), 8.84 (1H, br s), 12.06 (1H, br s).

EIMS m/z (relative intensity): 432 (M⁺), 200 (100).

Example 55 Compound No. 806 in Table

Production of 7-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 47 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless prism crystal.

Melting point: 189-192° C.

IR (KBr) cm⁻¹: 3139, 2925, 2854, 1668, 1561, 1523, 1435, 1401.

¹H-NMR (d₆-DMSO) δ: 1.39-1.52 (4H, m), 1.56-1.70 (2H, m), 1.75 (2H, quint, J=7.1 Hz), 2.28-2.34 (2H, m), 2.38 (3H, s), 2.40 (3H, s), 2.43 (3H, s), 3.27 (2H, t, J=7.1 Hz), 6.84 (1H, s), 7.07 (1H, t, J=7.1 Hz), 7.08 (1H, t, J=7.1 Hz), 7.32 (1H, d, J=7.1 Hz), 7.46 (1H, d, J=7.1 Hz), 8.79 (1H, br s).

EIMS m/z (relative intensity): 460 (M⁺), 150 (100).

Example 56 Compound No. 807 in Table

Production of 8-(benzimidazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 48 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 186-187° C.

IR (KBr) cm⁻¹: 3430, 3222, 2925, 1661, 1564, 1522, 1437, 808. ¹H-NMR (d₆-DMSO) δ: 1.35-1.43 (4H, m), 1.47 (2H, quint, J=7.2 Hz), 1.60-1.68 (2H, m), 1.76 (2H, quint, J=7.2 Hz), 2.23-2.32 (2H, m), 2.40 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 3.28 (2H, t, J=7.2 Hz), 6.89 (1H, s), 7.09 (1H, t, J=5.9 Hz), 7.09 (1H, t, J=5.9 Hz), 7.40 (1H, d, J=5.9 Hz), 7.41 (1H, d, J=5.9 Hz), 8.80 (1H, br s), 12.09 (1H, br s).

EIMS m/z (relative intensity): 474 (M⁺), 150 (100).

Example 57 Compound No. 813 in Table

Production of 4-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 4-bromobutanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless crystal.

Melting point: 123-125° C.

IR (KBr) cm⁻¹: 3436, 3239, 2974, 2929, 1656, 1502, 1454, 1130.

¹H-NMR (d₆-DMSO) δ: 1.23-1.28 (6H, m), 2.12-2.19 (2H, m), 2.43 (3H, s), 2.48-2.50 (2H, m), 2.93 (2H, q, J=7.1 Hz), 3.06 (2H, q, J=7.1 Hz), 3.41-3.48 (2H, m), 6.89 (3H, s), 7.29-7.34 (2H, m), 7.56-7.62 (2H, m), 8.96 (1H, br s).

EIMS m/z (relative intensity): 447 (M⁺), 227 (100).

Example 58 Compound No. 814 in Table

Production of 5-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 5-bromopentanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless needle crystal.

Melting point: 122-123° C.

¹H-NMR (d₆-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.76-1.87 (2H, m), 1.87-1.97 (2H, m), 2.29-2.40 (2H, m), 2.43 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.38 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.26-7.35 (2H, m), 7.55-7.60 (2H, m), 8.82 (1H, br s).

EIMS m/z (relative intensity): 461 (M⁺), 227 (100).

Example 59 (Compound No. 816 in Table)

Production of 7-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 7-bromoheptanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless needle crystal.

Melting point: 103-105° C.

IR (KBr) cm⁻¹: 3247, 1663, 1501, 1455.

¹H-NMR (d₆-DMSO) δ: 1.24 (3H, t, J=7.3 Hz), 1.25 (3H, t, J=7.3 Hz), 1.38-1.54 (4H, m), 1.57-1.72 (2H, m), 1.73-1.89 (2H, m), 2.19-2.32 (2H, m), 2.41 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.33 (2H, t, J=7.1 Hz), 6.86 (1H, s), 7.24-7.32 (2H, m), 7.52-7.60 (2H, m), 8.65 (1H, br s).

EIMS m/z (relative intensity): 489 (M⁺), 228 (100).

Example 60 (Compound No. 817 in Table)

Production of 8-(benzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 27 except that 8-bromooctanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless needle crystal.

Melting point: 82-84° C.

IR (KBr) cm⁻¹: 3449, 3245, 2932, 1669, 1500, 1455, 1132.

¹H-NMR (d₆-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.37-1.42 (4H, m), 1.48 (2H, quint, J=7.2 Hz), 1.60-1.67 (2H, m), 1.82 (2H, quint, J=7.2 Hz), 2.24-2.30 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz), 3.34 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.27-7.33 (2H, m), 7.56-7.61 (2H, m), 8.73 (1H, br s).

EIMS m/z (relative intensity): 503 (M⁺), 229 (100).

Example 61 (Compound No. 823 in Table)

Production of 4-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 57 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 119-120° C.

¹H-NMR (d₆-DMSO) δ: 1.25 (3H, t, J=7.4 Hz), 1.26 (3H, t, J=7.4 Hz). 2.07-2.23 (2H, m), 2.43 (3H, s), 2.45-2.55 (2H, m,), 2.93 (2H, q, J=7.4 Hz), 3.06 (2H, q, J=7.4 Hz), 3.41-3.54 (2H, m), 6.89 (1H, s), 7.35 (1H, t, J=8.1 Hz), 7.45 (1H, t, J=8.1 Hz), 7.83 (1H, d, J=8.1 Hz). 7.94 (1H, d, J=8.1 Hz), 8.95 (1H, br s).

EIMS m/z (relative intensity): 463 (M⁺), 229 (100).

Example 62 (Compound No. 824 in Table)

Production of 5-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 58 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 102-104° C.

¹H-NMR (d₆-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 1.77-1.88 (2H, m), 1.88-2.00 (2H, m), 2.29-2.41 (2H, m), 2.43 (3H, s), 2.93 (2H, q, J=7.3 Hz), 3.06 (2H, q, J=7.3 Hz), 3.41 (2H, t, J=7.0 Hz), 6.89 (1H, s), 7.35 (1H, ddd, J=8.2, 7.2, 1.2 Hz), 7.45 (1H, ddd, J=8.2, 7.2, 1.2 Hz), 7.84 (1H, dd, J=8.2, 1.2 Hz), 7.94 (1H, dd, J=8.2, 1.2 Hz), 8.84 (1H, br s).

EIMS m/z (relative intensity): 477 (M⁺), 229 (100).

Example 63 (Compound No. 826 in Table)

Production of 7-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 59 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting Point: 114-116° C.

IR (KBr) cm⁻¹: 3245, 1665, 1536, 1509, 1426.

¹H-NMR (d₆-DMSO) δ: 1.24 (3H, t, J=7.3 Hz), 1.25 (3H, t, J=7.3 Hz), 1.39-1.56 (4H, m), 1.58-1.71 (2H, m), 1.75-1.88 (2H, m), 2.19-2.31 (2H, m), 2.42 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.35 (2H, t, J=7.2 Hz), 6.86 (1H, s), 7.32 (1H, td, J=7.6, 1.2 Hz), 7.42 (1H, td, J=7.6, 1.2 Hz), 7.81 (1H, dd, J=7.6, 1.2 Hz), 7.91 (1H, dd, J=7.6, 1.2 Hz), 8.67 (1H, br s).

EIMS m/z (relative intensity): 505 (M⁺), 227 (100).

Example 64 (Compound No. 827 in Table)

Production of 8-(benzothiazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 60 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 94-96° C.

IR (KBr) cm⁻¹: 3433, 3243, 2929, 1669, 1511, 1428.

¹H-NMR (d₆-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz). 1.37-1.43 (4H, m), 1.45-1.52 (2H, m), 1.57-1.68 (2H, m), 1.82 (2H, quint, J=7.2 Hz), 2.20-2.32 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz), 3.37 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.34 (1H, td, J=7.6, 1.1 Hz), 7.44 (1H, td, J=7.6, 1.1 Hz), 7.83 (1H, dd, J=7.6, 1.1 Hz), 7.93 (1H, dd, J=7.6, 1.1 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 519 (M⁺), 227 (100).

Example 65 (Compound No. 833 in Table)

Production of 4-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 57 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale-yellow powdery crystal.

Melting point: 160-161° C.

¹H-NMR (d₆-DMSO) δ: 1.25 (3H, t, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz), 2.27-2.37 (2H, m), 2.44 (3H, s), 2.48-2.50 (2H, m), 2.93 (2H, q, J=7.3 Hz), 3.06 (2H, q, J=7.3 Hz), 3.34-3.46 (2H, m), 6.89 (1H, s), 7.05-7.14 (2H, m), 7.33 (1H, m), 7.46 (1H, m), 8.95 (1H, br s).

EIMS m/z (relative intensity): 446 (M⁺), 195 (100).

Example 66 (Compound No. 834 in Table)

Production of 5-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 58 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 163-165° C.

¹H-NMR (d₆-DMSO) δ: 1.23 (3H, t, J=7.3 Hz), 1.24 (3H, t, J=7.3 Hz), 1.74-1.88 (4H, m), 2.27-2.38 (2H, m), 2.41 (3H, s), 2.90 (2H, q, J=7.3 Hz), 3.03 (2H, q, J=7.3 Hz), 3.26-3.34 (2H, m), 6.86 (1H, s), 7.04-7.11 (2H, m), 7.32 (1H, m), 7.46 (1H, m), 8.79 (1H, br s).

EIMS m/z (relative intensity): 460 (M⁺), 195 (100).

Example 67 (Compound No. 836 in Table)

Production of 7-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 59 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 151-156° C.

IR (KBr) cm⁻¹: 3136, 3106, 1656, 1518, 1438, 1401, 1337, 1268.

¹H-NMR (d₆-DMSO) δ: 1.24 (3H, t, J=7.3 Hz), 1.25 (3H, t, J=7.3 Hz). 1.36-1.54 (4H, m), 1.55-1.82 (4H, m), 2.15-2.32 (2H, m), 2.41 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.26 (2H, t, J=7.3 Hz), 6.86 (1H, s), 7.03-7.11 (2H, m), 7.34-7.44 (2H, m), 8.67 (1H, br s).

EIMS m/z (relative intensity): 488 (M⁺), 151 (100).

Example 68 (Compound No. 837 in Table)

Production of 8-(benzimidazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 60 except that 2-mercaptobenzoimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 166-168° C.

IR (KBr) cm⁻¹: 3427, 3147, 2928, 1660, 1560, 1526, 1437.

¹H-NMR (d₆-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.36-1.41 (4H, m), 1.47 (2H, quint, J=7.2 Hz), 1.60-1.67 (2H, m), 1.75 (2H, quint, J=7.2 Hz), 2.22-2.32 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz,), 3.28 (2H, t, J=7.2 Hz), 6.85 (1H, s), 7.08 (1H, t, J=5.9 Hz), 7.09 (1H, t, J=5.9 Hz), 7.40 (1H, d, J=5.9 Hz), 7.41 (1H, d, J=5.9 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 502 (M⁺), 151 (100).

Example 69 (Compound No. 843 in Table)

Production of 4-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 4-bromobutanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless needle crystal.

Melting point: 128-129° C.

IR (KBr) cm⁻¹: 3448, 3235, 2962, 1683, 1657, 1555, 1515, 1500, 1456, 1131.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.6 Hz), 1.30 (6H, d, J=6.8 Hz). 2.10-2.17 (2H, m), 2.42 (3H, s), 2.47-2.50 (2H, m), 3.39-3.47 (2H, m), 3.55 (1H, sept, J=6.6 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.92 (1H, s), 7.28 (1H, td, J=7.3, 1.7 Hz), 7.30 (1H, td, J=7.3, 1.7 Hz), 7.56 (1H, dd, J=7.3, 1.7 Hz), 7.58 (1H, dd, J=7.3, 1.7 Hz), 8.90 (1H, br s).

EIMS m/z (relative intensity): 475 (M⁺), 207 (100).

Example 70 (Compound No. 844 in Table)

Production of 5-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 5-bromopentanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless prism crystal.

Melting point: 129-130° C.

IR (KBr) cm⁻¹: 3448, 3215, 3167, 2965, 1654, 1555, 1525, 1500, 1454, 1128.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 1.75-1.85 (2H, m), 1.86-1.96 (2H, m), 2.26-2.40 (2H, m), 2.42 (3H, s), 3.37 (2H, t, J=7.1 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.27 (1H, td, J=7.6, 1.7 Hz), 7.30 (1H, td, J=7.6, 1.7 Hz), 7.55 (1H, dd, J=7.6, 1.7 Hz), 7.58 (1H, dd, J=7.6, 1.7 Hz), 8.75 (1H, br s).

EIMS m/z (relative intensity): 489 (M⁺), 221 (100).

Example 71 (Compound No. 846 in Table)

Production of 7-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 7-bromoheptanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless needle crystal.

Melting point: 76-78° C.

IR (KBr) cm⁻¹: 3436, 3265, 2929, 1663, 1503, 1455.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.32 (6H, d, J=6.8 Hz), 1.43-1.54 (4H, m), 1.65 (2H, quint, J=7.2 Hz), 1.83 (2H, quint, J=7.2 Hz), 2.20-2.33 (2H, m), 2.43 (3H, s), 3.35 (2H, t, J=7.2 Hz), 3.56 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.27-7.34 (2H, m), 7.56-7.61 (2H, m), 8.72 (1H, br s).

EIMS m/z (relative intensity): 517 (M⁺), 249 (100).

Example 72 (Compound No. 847 in Table)

Production of 8-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 8-bromooctanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a colorless oil.

IR (KBr) cm⁻¹: 3241, 1664, 1559, 1526, 1501, 1454.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.34-1.54 (6H, m), 1.55-1.69 (2H, m), 1.73-1.89 (2H, m), 2.15-2.28 (2H, m), 2.42 (3H, s), 3.27 (2H, t, J=7.3 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.90 (1H, s), 7.24-7.32 (2H, m), 7.51-7.60 (2H, m), 8.59 (1H, br s).

EIMS m/z (relative intensity): 531 (M⁺), 263 (100).

Example 73 (Compound No. 848 in Table)

Production of 9-(benzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 9-bromononanoyl chloride was used instead of 6-bromohexanoyl chloride to obtain the desired compound as a pale yellow oil.

IR (Cap) cm⁻¹: 3243, 2962, 2927, 1668, 1558, 1505, 1455, 1130.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz) 1.31 (6H, d, J=6.8 Hz), 1.28-1.50 (8H, m), 1.55-1.65 (2H, m), 1.80 (2H, quint, J=7.3 Hz), 2.17-2.27 (2H, m), 2.42 (3H, s), 3.32 (2H, t, J=7.3 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.27 (1H, td, J=7.3, 1.7 Hz), 7.30 (1H, td, J=7.3, 1.7 Hz), 7.54-7.60 (2H, m), 8.65 (1H, br s).

EIMS m/z (relative intensity): 545 (M⁺), 277 (100).

Example 74 (Compound No. 851 in Table)

Production of 2-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 49 except that 2-bromo-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide was used instead of 2-bromo-N-2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide to obtain the desired compound as a colorless needle crystal.

Melting point: 117-118° C.

IR (KBr) cm⁻¹: 3431, 3179, 2967, 1660, 1559, 1526, 1428.

¹H-NMR (CDCl₃) δ: 1.19 (6H, d, J=6.7 Hz), 1.21 (6H, d, J=6.7 Hz), 2.41 (3H, s), 3.39 (1H, sept, J=6.7 Hz), 3.92 (1H, sept, J=6.7 Hz), 4.18 (2H, s), 6.68 (1H, s), 7.32 (1H, td, J=7.7, 1.2 Hz), 7.41 (1H, td, J=7.7, 1.2 Hz), 7.77 (1H, d, J=7.7 Hz), 7.91 (1H, d, J=7.7 Hz), 8.80 (1H, br s).

EIMS m/z (relative intensity): 463 (M⁺), 180 (100).

Elemental Analysis: as C₂₁H₂₅N₃OS₄; Calculated: C, 54.39; H, 5.43; N, 9.06; S, 27.66. Found: C, 54.28; H, 5.45; N, 8.93; S, 27.73.

Example 75 (Compound No. 853 in Table)

Production of 4-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 69 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 116-117° C.

IR (KBr) cm⁻¹: 3450, 3257, 2962, 1667, 1557, 1510, 1457, 1429, 987.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 2.08-2.17 (2H, m), 2.42 (3H, s), 2.43-2.47 (2H, m), 3.45 (2H, t, J=7.1 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.92 (1H, s), 7.33 (1H, t, J=7.8 Hz), 7.43 (1H, t, J=7.8 Hz), 7.81 (1H, d, J=7.8 Hz), 7.92 (1H, d, J=7.8 Hz), 8.90 (1H, br s).

EIMS m/z (relative intensity): 491 (M⁺), 69 (100).

Example 76 (Compound(No. 854 in Table)

Production of 5-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 70 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 107-109° C.

IR (KBr) cm⁻¹: 3441, 3215, 2963, 1656, 1557, 1523, 1460, 1429, 996.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 1.76-1.85 (2H, m), 1.86-1.96 (2H, m), 2.26-2.40 (2H, m), 2.42 (3H, s), 3.39 (2H, t, J=7.1 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.33 (1H, td, J=8.1, 1.2 Hz), 7.43 (1H, td, J=8.1, 1.2 Hz), 7.82 (1H, dd, J=8.1, 1.2 Hz), 7.92 (1H, dd, J=8.1, 1.2 Hz), 8.75 (1H, br s).

EIMS m/z (relative intensity): 505 (M⁺), 221 (100).

Example 77 (Compound No. 855 in Table)

Production of 6-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 84-86° C.

IR (KBr) cm⁻¹: 3436, 3212, 2961, 2925, 1655, 1555, 1522, 1428.

¹H-NMR (d₆-DMSO) δ: 1.30 (6H, d, J=6.6 Hz), 1.33 (6H, d, J=6.8 Hz), 1.54-1.62 (2H, m), 1.65-1.73 (2H, m), 1.85 (2H, quint, J=7.0 Hz), 2.22-2.33 (2H, m), 2.43 (3H, s), 3.38 (2H, t, J=7.0 Hz), 3.57 (1H, sept, J=6.6 Hz), 3.91 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.34 (1H, t, J=7.8 Hz), 7.44 (1H, t, J=7.8 Hz), 7.83 (1H, d, J=7.8 Hz), 7.93 (1H, d, J=7.8 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 519 (M⁺), 235 (100).

Example 78 (Compound No. 856 in Table)

Production of 7-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 71 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 74-76° C.

IR (KBr) cm⁻¹: 3436, 3200, 3158, 2961, 2928, 1654, 1525, 1427.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.6 Hz), 1.32 (6H, d, J=6.8 Hz), 1.43-1.55 (4H, m), 1.65 (2H, quint, J=7.2 Hz), 1.83 (2H, quint, J=7.2 Hz), 2.22-2.33 (2H, m), 2.43 (3H, s), 3.37 (2H, t, J=7.2 Hz), 3.56 (1H, sept, J=6.6 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.34 (1H, td, J=7.7, 1.2 Hz), 7.44 (1H, td, J=7.7, 1.2 Hz), 7.83 (1H, dd, J=7.7, 1.2 Hz), 7.94 (1H, dd, J=7.7, 1.2 Hz), 8.68 (1H, br s).

EIMS m/z (relative intensity): 533 (M⁺), 249 (100).

Example 79 (Compound No. 857 in Table)

Production of 8-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 72 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless neddle crystal.

Melting point: 107-108° C.

IR (KBr) cm⁻¹: 3239, 1664, 1559, 1526, 1456, 1428.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.34-1.54 (6H, m), 1.55-1.70 (2H, m), 1.73-1.88 (2H, m), 2.15-2.29 (2H, m), 2.42 (3H, s), 3.35 (2H, t, J=7.3 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.90 (1H, s), 7.31 (1H, t, J=7.8 Hz), 7.42 (1H, t, J=7.8 Hz), 7.81 (1H, d, J=7.8 Hz), 7.90 (1H, d, J=7.8 Hz), 8.59 (1H, br s).

EIMS m/z (relative intensity): 547 (M⁺), 263 (100).

Example 80 (Compound No. 858 in Table)

Production of 9-(benzothiazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 73 except that 2-mercaptobenzothiazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow oil.

IR (Cap) cm⁻¹: 3243, 2962, 2927, 1668, 1559, 1526, 1456.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.28-1.50 (8H, m), 1.55-1.65 (2H, m), 1.80 (2H, quint, J=7.0 Hz), 2.17-2.27 (2H, m), 2.42 (3H, s), 3.34 (2H, t, J=7.0 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.32 (1H, td, J=7.1, 1.2 Hz), 7.43 (1H, td, J=7.1, 1.2 Hz), 7.81 (1H, dd, J=7.1, 1.2 Hz), 7.91 (1H, dd, J=7.1, 1.2 Hz), 8.65 (1H, br s).

EIMS m/z (relative intensity): 561 (M⁺), 277 (100).

Example 81 (Compound No. 861 in Table)

Production of 2-(benzimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 53 except that 2-bromo-N-[2,4-bis(isopropylthio)-6-methylpyridyl]acetamide was used instead of 2-bromo-N-[2,4-bis(methylthio)-6-methylpyridyl]acetamide to obtain the desired compound as a colorless needle crystal.

Melting point: 223-224° C.

IR (KBr) cm⁻¹: 3437, 3138, 3106, 2960, 1668, 1534, 1414.

¹H-NMR (CDCl₃) δ: 1.22 (6H, d, J=6.8 Hz), 1.25 (6H, d, J=6.8 Hz), 2.42 (3H, s), 3.41 (3H, sept, J=6.8 Hz), 3.95 (1H, sept, J=6.8 Hz), 4.05 (2H, H), 6.69 (1H, s), 7.18 (1H, t, J=6.1 Hz), 7.19 (1H, t, J=6.1 Hz), 7.34 (5H, br s), 7.62 (1H, br s), 9.33 (1H, br s), 10.61 (1H, br s).

EIMS m/z (relative intensity): 446 (M⁺), 371 (100).

Elemental analysis: as C₂₁H₂₆N₄OS₃; calculated: C, 56.47; H, 5.87; N, 12.54. found: C, 56.42; H, 5.87; N, 12.56.

Example 82 (Compound No. 863 in Table)

Production of 4-(benzomidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 69 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale-yellow powdery crystal.

Melting point: 209-211° C.

IR (KBr) cm⁻¹: 3480, 3196, 2963, 1664, 1557, 1529, 1428.

¹H-NMR (d₆-DMSO) δ: 1.25 (6H, d, J=6.8 Hz), 1.28 (6H, d, J=6.8 Hz). 2.04 (2H, quint, J=7.1 Hz), 2.43 (3H, s), 2.44 (2H, t, J=7.1 Hz), 3.36 (2H, t, J=7.1 Hz). 3.61 (1H, sept, J=6.8 Hz), 3.86 (1H, sept, J=6.8 Hz), 6.96 (1H, s), 7.09 (1H, dd, J=7.3, 5.4 Hz), 7.12 (1H, dd, J=7.3, 5.4 Hz), 7.35 (1H, m), 7.49 (1H, m), 9.38 (1H, s), 12.53 (1H, s).

EIMS m/z (relative intensity): 474 (M⁺), 207 (100).

Example 83 (Compound No. 864 in Table)

Production of 5-(benzimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 70 except that 2-mercaptobenimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 175-176° C.

IR (KBr) cm⁻¹: 3447, 3195, 2965, 1663, 1557, 1526, 1428, 1400.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 1.75-1.90 (4H, m), 2.26-2.38 (2H, m), 2.42 (3H, s), 3.30 (2H, t, J=7.1 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.07 (1H, t, J=6.1 Hz), 7.08 (1H, t, J=6.1 Hz), 7.32 (1H, d, J=6.1 Hz), 7.46 (1H, d, J=6.1 Hz), 8.72 (1H, br s).

EIMS m/z (relative intensity): 488 (M⁺), 221 (100).

Example 84 (Compound No. 865 in Table)

Production of 6-(benzimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 175-176° C.

¹H-NMR (d₆-DMSO) δ: 1.30 (6H, d, J=6.7 Hz), 1.32 (6H, d, J=6.7 Hz), 1.47-1.61 (2H, m), 1.62-1.72 (2H, m), 1.73-1.84 (2H, m), 2.18-2.35 (2H, m), 2.43 (3H, s), 3.21-3.33 (2H, m), 3.55 (1H, sept, J=6.7 Hz), 3.90 (1H, sept, J=6.7 Hz), 6.92 (1H, s), 7.03-7.12 (2H, m), 7.33 (1H, m), 7.47 (1H, m), 8.75 (1H, br s), 12.05 (1H, br s).

EIMS m/z (relative intensity): 502 (M⁺), 235 (100).

Example 85 (Compound No. 866 in Table)

Production of 7-(benzoimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 71 except that 2-mercaptobenzoimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale-yellow needle crystal.

Melting point: 118-121° C.

IR (KBr) cm⁻¹: 3393, 3219, 2963, 2928, 1663, 1559, 1526, 1439.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.6 Hz), 1.32 (6H, d, J=6.8 Hz), 1.41-1.53 (4H, m), 1.64 (2H, quint, J=7.2 Hz), 1.76 (2H, quint, J=7.2 Hz), 2.18-2.33 (2H, m), 2.43 (3H, s), 3.28 (2H, t, J=7.2 Hz), 3.56 (1H, sept, J=6.6 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.08 (1H, t, J=5.9 Hz), 7.09 (1H, t, J=5.9 Hz), 7.40 (1H, d, J=5.9 Hz), 7.41 (1H, d, J=5.9 Hz), 8.86 (1H, br s).

EIMS m/z (relative intensity): 516 (M⁺), 399 (100).

Example 86 (Compound No. 867 in Table)

Production of 8-(benzimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 72 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 170-171° C.

IR (KBr) cm⁻¹: 3158, 2963, 2930, 1665, 1559, 1526, 1508, 1429.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz) 1.32-1.50 (6H, m), 1.56-1.66 (2H, m), 1.74 (2H, quint, J=7.3 Hz), 2.17-2.27 (2H, m), 2.42 (3H, s), 3.26 (2H, t, J=7.3 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.05-7.10 (2H, m), 7.32 (1H, m), 7.45 (1H, m), 8.65 (1H, br s).

EIMS m/z (relative intensity): 530 (M⁺), 413 (100).

Example 87 (Compound No. 868 in Table)

Production of 9-(benzimidazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 73 except that 2-mercaptobenzimidazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale brown powdery crystal.

Melting point: 112-114° C.

IR (KBr) cm⁻¹: 3435, 3185, 2927, 1660, 1558, 1526, 1437.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz) 1.31 (6H, d, J=6.8 Hz), 1.28-1.48 (8H, m), 1.52-1.65 (2H, m), 1.73 (2H, quint, J=7.1 Hz), 2.18-2.28 (2H, m), 2.42 (3H, s), 3.25 (2H, t, J=7.1 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.07 (1H, t, J=6.1 Hz), 7.08 (1H, t, J=6.1 Hz), 7.32 (1H, d, J=6.1 Hz), 7.46 (1H, d, J=6.1 Hz), 8.80 (1H, br s), 12.05 (1H, br s).

EIMS m/z (relative intensity): 544 (M⁺), 151 (100).

Example 88 (Compound No. 1145 in Table)

Production of 6-(benzoxazole-2-ylthio)-N-[2-methyl-4,6-bis(methylthio)-5-pyrimidyl)hexanamide:

4,6-Dihydroxy-2-methylpyrimidine (1.0 g, 7.9 mmol) was added gradualy to ice-cooled fuming nitric acid (3 ml) stirring. The mixture was stirred for 2 hours cooling with ice and for 1 hour at the room temperature, and then the precipitated crystal was filtered and dried to obtain 207 mg (yield 15%) of 4,6-dihydroxy-2-methyl-5-nitropyrimidine.

This nitropyrimidine (205 mg, 1.2 mmol) was dissolved in phosphoryl chloride (1 ml) and diethylaniline (0.3 ml, 1.9 mmol) was added thereto, and the mixture was stirred for 1 hour at 100° C. and for 1 hour at 120° C. The reaction solution was added to ice and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate=20:1) to obtain 194 mg (yield 77%) of 4,6-dichloro-2-methyl-5-nitropyrimidine as a colorless needle crystal.

And then a methanol (10 mml) solution of 4,6-dichloro-2-methyl-5-nitropyrimidine (1.0 g, 4.81 mmol) was added dropwise to a methanol (10 ml) solution of sodium thiomethoxide (780 mg, 10.6 mmol) while being cooled with ice, and after the mixture was stirred for 1 hour while being cooled with ice, water added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was recrystalized with ethyl acetate-hexan to obtain 609 mg (yield 55%) of 4,6-bis(methylthio)-2-methyl-5-nitropyrimidine.

Potassium carbonate (119 mg, 0.865 mmol) and pratinum dioxide (40 mg, 0.18 mmol) were added to ethanol (100 ml) solution of this nitropyrimidine (100 mg, 0.43 mmol) and stirred in hydrogen. After 1.5 hours, the reaction mixture was filtered, the filtrate was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate 6:1) to obtain 66 mg (yield 76%) of 5-amino-4,6-bis(methylthio)-2-methylpyrimidine.

And then the reaction and the treatment were conducted in the same manner as in Example 18 except that 5-amino-4,6-bis(methylthio)-2-methylthiopyrimidine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

Melting point: 148-151° C.

IR (KBr) cm⁻¹: 3440, 3245, 2929, 1660, 1530.

¹H-NMR (CDCl₃) δ: 1.43-1.55 (2H, m), 1.57-1.69 (2H, m), 1.72-1.84 (2H, m), 2.14-2.29 (2H, m), 2.38 (6H, s), 2.48 (3H, m), 3.28 (2H, t, J=7.3 Hz), 7.21 (1H, td, J=7.4, 1.7 Hz), 7.24 (1H, td, J=7.4, 1.7 Hz), 7.49 (1H, dd, J=7.4 Hz), 7.51 (1H, dd, J=7.4, 1.7 Hz), 8.91 (1H, br s).

EIMS m/z (relative intensity): 448 (M⁺, 100).

Example 89 (Compound No. 1247 in Table)

Production of 2-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 49 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 207-209° C.

IR (KBr) cm⁻¹: 3435, 3235, 1673, 1509, 1433, 1329, 1130.

¹H-NMR (CDCl₃) δ: 2.32 (3H, s), 2.41 (3H, s), 2.48 (3H, s), 4.14 (2H, s), 6.81 (1H, s), 7.41 (1H, t, J=7.8 Hz), 7.52 (1H, d, J=7.8 Hz), 7.79 (1H, d, J=7.8 Hz), 8.46 (1H, br s).

EIMS m/z (relative intensity): 459 (M⁺), 227 (100).

Elemental analysis: as C₁₈H₁₆F₃N₃O₂S₃; Calculated: C, 47.05; H, 3.51; N, 9.14. Found: C, 46.84; H, 3.66; N, 9.03.

Example 90 (Compound No. 1250 in Table)

Production of 5-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 46 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 179-180° C.

¹H-NMR (d₆-DMSO) δ: 1.75-1.87 (2H, m), 1.87-2.00 (2H, m), 2.37 (3H, s), 2.39 (3H, s), 2.30-2.39 (2H, m), 2.43 (3H, s), 3.36-3.46 (2H, m), 6.84 (1H, s), 7.50 (1H, t, J=7.9 Hz), 7.59 (1H, d, J=7.9 Hz). 7.89 (1H, d, J=7.9 Hz), 8.85 (1H, br s).

EIMS m/z (relative intensity): 501 (M⁺), 200 (100).

Example 91 (Compound No. 1252 in Table)

Production of 7-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 47 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 129-131° C.

IR (KBr) cm⁻¹: 3247, 1662, 1505, 1435, 1337, 1128.

¹H-NMR (d₆-DMSO) δ: 1.40-1.55 (4H, m), 1.60-1.71 (2H, m), 1.80-1.89 (2H, m), 2.20-2.34 (2H, m), 2.38 (3H, s), 2.40 (3H, s), 2.44 (3H, s), 3.37 (2H, t, J=7.1 Hz), 6.84 (1H, s), 7.49 (1H, t, J=7.8 Hz), 7.58 (1H, d, J=7.8 Hz), 7.88 (1H, d, J=7.8 Hz), 8.78 (1H, br s).

EIMS m/z (relative intensity): 529 (M⁺), 200 (100).

Example 92 (Compound No. 1253 in Table)

Production of 8-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 48 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 115-116° C.

¹H-NMR (d₆-DMSO) δ: 1.40-1.54 (6H, m), 1.56-1.72 (2H, m), 1.85 (2H, quint, J=7.0 Hz), 2.18-2.36 (2H, m), 2.40 (3H, s), 2.43 (3H, s), 2.46 (3H, s), 3.38 (2H, t, J=7.3 Hz), 6.86 (1H, s), 7.51 (1H, t, J=7.5 Hz), 7.60 (1H, d, J=7.5 Hz), 7.90 (1H, d, J=7.5 Hz), 8.16 (1H, br s).

EIMS m/z (relative intensity): 543 (M⁺), 200 (100).

Example 93 (Compound No. 1260 in Table)

Production of 5-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 46 except that 5-chloro-7-isopropyl-2-mercapto-4-metylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 155-156° C.

¹H-NMR (d₆-DMSO) δ: 1.31 (6H, d, J=7.1 Hz), 1.72-1.85 (2H, m), 1.85-1.98 (2H, m), 2.36 (3H, s), 2.39 (3H, s), 2.32-2.40 (2H, m), 2.43 (3H, s), 2.46 (3H, s), 3.22 (1H, sept, J=7.1 Hz), 3.31-3.42 (2H, m), 6.84 (1H, s), 7.13 (1H, s), 8.73 (1H, br s).

EIMS m/z (relative intensity): 525 (M⁺: ^(37 Cl),) 523 (M³⁰ : ³⁵Cl), 200 (100).

Example 94 (Compound No. 1262 in Table)

Production of 7-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 47 except that 5-chloro-7-isopropyl-2-mercapto-4-metylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless prism crystal.

Melting point: 129-131° C.

IR (KBr) cm⁻¹: 3413, 3241, 2964, 2924, 1655, 1567, 1505, 1490, 1435, 1149.

¹H-NMR (d₆-DMSO) δ: 1.31 (6H, d, J=7.1 Hz), 1.40-1.55 (4H, m), 1.56-1.70 (2H, m), 1.83 (2H, quint, J=7.1 Hz), 2.30 (2H, t, J=7.1 Hz), 2.38 (3H, s), 2.40 (3H, s), 2.41 (3H, s), 2.46 (3H, s), 3.21 (1H, sept, J=7.1 Hz), 3.34 (2H, t, J=7.1 Hz), 6.84 (1H, s), 7.14 (1H, s), 8.51 (1H, br s).

EIMS m/z (relative intensity): 553 (M⁺: ³⁷Cl) 551 (M⁺: ³⁵Cl), 200 (100).

Example 95 (Compound No. 1260 in Table)

Production of 8-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 48 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 128-131° C.

IR (KBr) cm⁻¹: 3423, 3231, 2929, 1662, 1504, 1489.

¹H-NMR (d₆-DMSO) δ: 1.32 (6H, d, J=7.0 Hz), 1.38-1.43 (4H, m), 1.49 (2H, quint, J=7.2 Hz), 1.60-1.69 (2H, m), 1.84 (2H, quint, J=7.2 Hz), 2.23-2.33 (2H, m), 2.40 (3H, s), 2.42 (3H, s), 2.45 (3H, s), 2.47 (3H, s), 3.23 (1H, sept, J=7.0 Hz), 3.35 (1H, t, J=7.2 Hz), 6.86 (1H, s), 7.15 (1H, s), 8.78 (1H, br s).

EIMS m/z (relative intensity): 567 (M⁺; ³⁷Cl), 565 (M⁺; ³⁵Cl), 200 (100).

Example 96 (Compound No. 1267 in Table)

Production of 2-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 89 except that 3-amino-2,4-bis(ethylthio)-6-methylpyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless prism crystal.

Melting point: 182-183° C.

IR (KBr) cm⁻¹: 3435, 3244, 1663, 1508, 1432, 1332.

¹H-NMR (CDCl₃) δ: 1.16 (3H, t, J=7.4 Hz), 1.20 (3H, t, J=7.4 Hz), 2.42 (3H, s), 2.81 (2H, q, J=7.4 Hz), 3.03 (2H, q, J=7.4 Hz), 4.14 (2H, s), 6.63 (1H, s), 7.40 (1H, t, J=7.8 Hz), 7.52 (1H, d, J=7.8 Hz), 7.68 (1H, d, J=7.8 Hz), 8.34 (1H, br s).

EIMS m/z (relative intensity): 487 (M⁺), 235 (100).

Elemental Analysis: C₂₀H₂₀F₃N₃O₂S₃; Calculated: C, 49.27; H, 4.13; N, 8.62; F, 11.69. Found: C, 49.41; H, 4.20; N, 8.62; F, 11.59.

Example 97 (Compound No. 1269 in Table)

Production of 4-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 57 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 148-150° C.

IR (KBr) cm⁻¹: 3439, 3256, 2975, 2929, 1656, 1509, 1433, 1332, 1125.

¹H-NMR (d₆-DMSO) δ: 1.23 (3H, t, J=7.3 Hz), 1.24 (3H, t, J=7.3 Hz), 2.04-2.22 (2H, m), 2.42 (3H, s), 2.47-2.48 (2H, m), 2.92 (2H, q, J=7.3 Hz), 3.04 (2H, q, J=7.3 Hz), 3.42-3.51 (2H, m), 6.87 (1H, s), 7.51 (1H, t, J=7.8 Hz) 7.59 (1H, d, J=7.8 Hz), 7.89 (1H, d, J=7.8 Hz), 8.95 (1H, br s).

EIMS m/z (relative intensity): 515 (M⁺), 227 (100).

Example 98 (Compound No. 1270 in Table)

Production of 5-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 58 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 155-156° C.

¹H-NMR (d₆-DMSO) δ: 1.20-1.30 (6H, m), 1.73-2.05 (4H, m), 2.30-2.41 (2H, m), 2.42 (3H, s), 2.85-3.00 (2H, m), 3.01-3.09 (2H, m), 3.37-3.48 (2H, m), 6.88 (1H, s), 7.51 (1H, t, J=7.5 Hz), 7.60 (1H, d, J=7.5 Hz), 7.90 (1H, d, J=7.5 Hz), 8.75 (1H, br s).

EIMS m/z (relative intensity): 529 (M⁺), 227 (100).

Example 99 (Compound No. 1272 in Table)

Production of 7-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 59 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 127-128° C.

IR (KBr) cm⁻¹: 3448, 1659, 1506, 1336, 1128, 1116.

¹H-NMR (d₆-DMSO) δ: 1.24 (3H, t, J=7.3 Hz), 1.25 (3H, t, J=7.3 Hz), 1.39-1.56 (4H, m), 1.56-1.72 (2H, m), 1.78-1.91 (2H, m), 2.19-2.33 (2H, m), 2.42 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.33 Hz), 3.37 (2H, t, J=7.2 Hz), 6.86 (1H, s), 7.49 (1H, t, J=7.9 Hz), 7.58 (1H, d, J=7.9 Hz), 7.88 (1H, d, J=7.9 Hz), 8.67 (1H, br s).

EIMS m/z (relative intensity): 557 (M⁺), 227 (100).

Example 100 (Compound No. 1273 in Table)

Production of 8-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 60 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless crystal.

Melting point: 99-100° C.

IR (KBr) cm⁻¹: 3425, 3245, 2923, 1655, 1509, 1433, 1332, 1125.

¹H-NMR (d₆-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.38-1.43 (4H, m), 1.49 (2H, quint, J=7.2 Hz), 1.60-1.68 (2H, m), 1.85 (2H, quint, J=7.2 Hz), 2.20-2.30 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.06 (2H, q, J=7.3 Hz), 3.38 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.51 (1H, t, J=7.8 Hz), 7.60 (1H, d, J=7.8 Hz), 7.90 (1H, d, J=7.8 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 571 (M⁺), 227 (100).

Example 101 (Compound No. 1274 in Table)

Production of 9-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 28 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole t o obtain the desired compound as a colorless powdery crystal.

Melting point: 115-116° C.

¹H-NMR (d6-DMSO) δ: 1.26 (3H, t, J=7.2 Hz), 1.27 (3H, t, J=7.2 Hz), 1.31-1.55 (8H, m), 1.57-1.69 (2H, m), 1.84 (2H, quint, J=6.9 Hz), 2.18-2.34 (2H, m), 2.43 (3H, s), 2.94 (2H, q, J=7.2 Hz), 3.06 (2H, q, J=7.2 Hz), 3.37 (2H, t, J=7.3 Hz), 6.88 (1H, s), 7.51 (1H, t, J=8.4 Hz), 7.61 (1H, d, J=8.4 Hz), 7.90 (1H, d, J=8.4 Hz), 8.73 (1H, br s).

EIMS m/z (relative intensity): 585 (M⁺) 227 (100).

Example 102 (Compound No. 1279 in Table)

Production of 4-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 57 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 122-123° C.

IR (KBr) cm⁻¹: 3258, 1665, 1502, 1145.

¹H-NMR (d₆-DMSO) δ: 1.23 (3H, t, J=7.3 Hz), 1.24 (3H, t, J=7.3 Hz), 1.31 (6H, d, J=6.8 Hz), 2.15 (2H, t, J=7.0 Hz), 2.42 (3H, s), 2.46 (3H, s), 2.47-2.50 (2H, m), 2.92 (2H, q, J=7.3 Hz), 3.04 (2H, q, J=7.3 Hz), 3.22 (1H, sept, J=6.8 Hz), 3.43 (2H, t, J=7.0 Hz), 6.87 (1H, s), 7.14 (1H, s), 8.83 (1H, br s).

EIMS m/z (relative intensity): 559 (M⁺: ³⁷Cl), 557 (M⁺: ³⁵Cl), 227 (100).

Example 103 (Compound No. 1280 in Table)

Production of 5-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 58 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 141-142° C.

¹H-NMR (d6-DMSO) δ: 1.25 (3H, t, J=7.4 Hz), 1.26 (3H, t, J=7.4 Hz), 1.32 (6H, d, J=6.9 Hz), 1.75-1.86 (2H, m), 1.87-2.00 (2H, m), 2.30-2.40 (2H, m), 2.43 (3H, s), 2.45-2.52 (3H, s), 2.92 (2H, q, J=7.4 Hz), 3.04 (2H, q, J=7.4 Hz), 3.23 (1H, sept, J=6.9 Hz), 3.33-3.43 (2H, m), 6.88 (1H, s), 7.15 (1H, s), 8.82 (1H, br s).

EIMS m/z (relative intensity): 553 (M⁺; ³⁷Cl), 551 (M⁺; ³⁵Cl), 227 (100).

Example 104 (Compound No. 1282 in Table)

Production of 7-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 59 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless prism crystal.

Melting point: 117-120° C.

IR (KBr) cm⁻¹: 3320, 1668, 1506, 1482, 1150.

¹H-NMR (d₆-DMSO) δ: 1.24 (3H, t, J=7.3 Hz), 1.25 (3H, t, J=7.3 Hz), 1.31 (6H, d, J=6.8 Hz), 1.39-1.57 (4H, m), 1.57-1.71 (2H, m), 1.77-1.89 (2H, m), 2.19-2.30 (2H, m), 2.42 (3H, s), 2.46 (3H, s), 2.92 (2H, q, J=7.3 Hz), 3.05 (2H, q, J=7.3 Hz), 3.21 (1H, sept, J=6.8 Hz), 3.33 (2H, t, J=7.2 Hz), 6.86 (1H, s), 7.13 (1H, s), 8.66 (1H, br s).

EIMS m/z (relative intensity): 581 (M⁺: ³⁷Cl), 579 (M⁺: ³⁵Cl), 227 (100).

Example 105 (Compound No. 1283 in Table)

Production of 8-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 60 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 82-84° C.

IR (KBr) cm⁻¹: 3435, 3259, 2929, 1655, 1504, 1490.

¹H-NMR (d₆-DMSO) δ: 1.26 (3H, t, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz), 1.32 (6H, d, J=6.8 Hz), 1.39-1.43 (4H, m), 1.49 (2H, quint, J=7.2 Hz), 1.60-1.68 (2H, m), 1.84 (2H, quint, J=7.2 Hz), 2.22-2.32 (2H, m), 2.43 (3H, s), 2.47 (3H, s), 2.94 (2H, q, J=7.3 Hz), 3.06 (2H, q, J=7.3 Hz), 3.22 (1H, sept, J=6.8 Hz), 3.35 (2H, t, J=7.2 Hz), 6.88 (1H, s), 7.15 (1H, s), 8.73 (1H, br s).

EIMS m/z (relative intensity): 595 (M⁺; ³⁷Cl), 593 (M⁺; ³⁵Cl),

Example 106 (Compound No. 1284 in Table)

Production of 9-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 28 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless powdery crystal.

Melting point: 93-94° C.

¹H-NMR (d₆-DMSO) δ: 1.27 (3H, t, J=7.3 Hz), 1.28 (3H, t, J=7.3 Hz), 1.32 (6H, d, J=7.0 Hz), 1.29-1.55 (8H, m), 1.56-1.69 (2H, m), 1.83 (2H, quint, J=6.9 Hz), 2.07-2.17 (2H, m), 2.43 (3H, s), 2.45-2.49 (3H, m), 2.94 (2H, q, J=7.3 Hz), 3.07 (2H, q, J=7.3 Hz), 3.22 (1H, sept, J=7.0 Hz), 3.34 (2H, t, J=7.3 Hz), 6.88 (1H, s), 7.15 (1H, s), 8.73 (1H, br s).

EIMS m/z (relative intensity): 609 (M⁺; ³⁷Cl), 607 (M⁺; ³⁵Cl), 229 (100).

Example 107 (Compound No. 1287 in Table)

Production of 2-(7-triffluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 89 except that 2-bromo-N-[2,4-bis(isopropylthio)-6-methylpyridyl]amide was used instead of 2-bromo-[2,4-bis(methylthio)-6-methylpyridyl]acetamide to obtain the desired compound as a colorless needle crystal.

Melting point: 121-122° C.

IR (KBr) cm⁻¹: 3426, 3210, 2967, 1655, 1507, 1431, 1329.

¹H-NMR (CDCl₃) δ: 1.17 (6H, d, J=6.8 Hz), 1.19 (6H, d, J=6.8 Hz), 2.42 (3H, s), 3.39 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 4.13 (2H, s), 6.68 (1H, s), 7.41 (1H, t, J=7.9 Hz), 7.52 (1H, d, J=7.9 Hz), 7.80 (1H, d, J=7.9 Hz), 8.30 (1H, br s).

EIMS m/z (relative intensity): 515 (M⁺), 181 (100).

Elemental analysis: as C₂₂H₂₄F₃N₃O₂S₃; Calculated: C, 51.25; H, 4.69; N, 8.15; F, 11.05. Found: C, 51.28; H, 4.73; N, 8.07; F, 11.02.

Example 108 (Compound No. 1289 in Table)

Production of 4-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 69 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless prism crystal.

Melting point: 135-136° C.

IR (KBr) cm⁻¹: 3446, 3255, 2968, 1660, 1559, 1531, 1504, 1491, 1433, 1139.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.29 (6H, d, J=6.8 Hz), 2.13-2.21 (2H, m), 2.42 (3H, s), 2.47-2.50 (2H, m), 3.44-3.50 (2H, m), 3.55 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.92 (1H, s), 7.51 (1H, t, J=7.8 Hz), 7.59 (1H, d, J=7.8 Hz), 7.88 (1H, d, J=7.8 Hz), 8.91 (1H, br s).

EIMS m/z (relative intensity): 543 (M⁺), 207 (100).

Example 109 (Compound No. 1290 in Table)

Production of 5-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 70 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 118-120° C.

IR (KBr) cm⁻¹: 3208, 3163, 1663, 1506, 1431, 1328, 1139.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 1.73-1.87 (2H, m), 1.87-2.01 (2H, m), 2.23-2.38 (2H, m), 2.41 (3H, s), 3.41 (2H, t, J=7.0 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.49 (1H, t, J=7.9 Hz), 7.58 (1H, d, J=7.9 Hz), 7.88 (1H, d, J=7.9 Hz), 8.67 (1H, br s).

EIMS m/z (relative intensity): 557 (M⁺), 221 (100).

Example 110 (Compound No. 1291 in Table)

Production of 6-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 102-103° C.

IR (KBr) cm⁻¹: 3136, 1648, 1507, 1431, 1332, 1129.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.49-1.76 (4H, m), 1.77-1.94 (2H, m), 2.19-2.32 (2H, m), 2.42 (3H, s), 3.38 (2H, t, J=7.3 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.49 (1H, t, J=7.8 Hz), 7.58 (1H, d, J=7.8 Hz), 7.87 (1H, d, J=7.8 Hz), 8.62 (1H, br s).

EIMS m/z (relative intensity): 571 (M⁺), 235 (100).

Example 111 (Compound No. 1292 in Table)

Production of 7-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 71 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzothiazole to obtain the desired compound as a colorless crystal.

Melting point: 76-78° C.

IR (KBr) cm⁻¹: 3423, 3268, 2931, 1660, 1506, 1433, 1334.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.43-1.54 (4H, m), 1.61-1.69 (2H, m), 1.86 (2H, quint, J=7.2 Hz), 2.18-2.32 (2H, m), 2.43 (3H, s), 3.39 (2H, t, J=7.2 Hz), 3.56 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.51 (1H, dd, J=8.1, 7.8 Hz), 7.60 (1H, d, J=7.8 Hz). 7.90 (1H, d, J=8.1 Hz), 8.68 (1H, br s).

EIMS m/z (relative intensity): 585 (M⁺), 249 (100).

Example 112 (Compound No. 1293 in Table)

Production of 8-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 72 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow oil.

IR (Cap) cm⁻¹: 3246, 2964, 2930, 1664, 1559, 1506, 1432.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.30 (6H, d, J=6.8 Hz), 1.32-1.50 (6H, m), 1.56-1.66 (2H, m), 1.83 (2H, quint, J=7.1 Hz), 2.17-2.27 (2H, m), 2.42 (3H, s), 3.36 (2H, t, J=7.1 Hz), 3.55 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.50 (1H, t, J=7.8 Hz), 7.59 (1H, d, J=7.8 Hz), 7.88 (1H, d, J=7.8 Hz), 8.65 (1H, br s).

EIMS m/z (relative intensity): 599 (M⁺), 263 (100)

Example 113 (Compound No. 1294 in Table)

Production of 9-(7-trifluoromethylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 73 except that 2-mercapto-7-trifluoromethylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale-yellow powdery crystal.

Melting point: 97-98° C.

IR (KBr) cm⁻¹: 3446, 3266, 2928, 1661, 1560, 1506, 1335, 1127.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.6 Hz), 1.30 (6H, d, J=6.8 Hz) 1.28-1.51 (8H, m), 1.55-1.64 (2H, m), 1.83 (2H, quint, J=7.3 Hz), 2.20-2.30 (2H, m), 2.42 (3H, s), 3.36 (2H, t, J=7.3 Hz), 3.55 (1H, sept, J=6.6 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.50 (1H, t, J=7.8 Hz), 7.59 (1H, d, J=7.8 Hz), 7.89 (1H, d, J=7.8 Hz), 8.71 (1H, br s).

EIMS m/z (relative intensity): 613 (M⁺), 277 (100).

Example 114 (Compound No. 1299 in Table)

Production of 4-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]butanamide:

The reaction and the treatment were conducted in the same manner as in Example 69 except that 5-chloro-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 141-143° C.

¹H-NMR (d₆-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 2.03-2.21 (2H, m), 2.42 (3H, s), 2.43-2.50 (5H, m), 3.22 (1H, sept, J=6.8 Hz), 3.38-3.48 (2H, m), 3.55 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.92 (1H, s), 7.14 (1H, s), 8.87 (1H, br s).

EIMS m/z (relative intensity): 567 (M⁺: ³⁷Cl), 565 (M⁺: ³⁵Cl), 207 (100).

Example 115 (Compound No. 1300 in Table)

Production of 5-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]pentanamide:

The reaction and the treatment were conducted in the same manner as in Example 70 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 143-145° C.

IR (KBr) cm⁻¹: 3231, 2924, 1720, 1657, 1508, 1297.

¹H-NMR (d6-DMSO) δ: 1.27 (6H, d, J=6.8 Hz), 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.73-1.85 (2H, m), 1.85-1.98 (2H, m), 2.25-2.37 (2H, m), 2.41 (3H, s), 2.43-2.50 (3H, s), 3.21 (1H, sept, J=6.8 Hz), 3.37 (2H, t, J=7.2 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.88 (1H, sept, J=6.8 Hz), 6.92 (1H, s), 7.14 (1H, s), 8.76 (1H, br s).

EIMS m/z (relative intensity): 581 (M⁺: ³⁷Cl), 579 (M⁺: ³⁵Cl, 100).

Example 116 (Compound No. 1301 in Table)

Production of 6-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 36 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 99-101° C.

IR (KBr) cm⁻¹: 3413, 3224, 2964, 1663, 1506, 1148.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.32 (12H, d, J=6.8 Hz), 1.54-1.62 (2H, m), 1.70 (2H, quint, J=7.1 Hz), 1.87 (2H, quint, J=7.1 Hz), 2.22-2.33 (2H, m). 2.43 (3H, s), 2.48 (3H, s), 3.23 (1H, sept, J=6.8 Hz), 3.36 (2H, t, J=7.1 Hz), 3.57 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.15 (1H, s), 8.72 (1H, br s).

EIMS m/z (relative intensity): 595 (M⁺; ³⁷Cl), 593 (M⁺; ³⁵Cl), 518 (100).

Example 117 (Compound No. 1302 in Table)

Production of 7-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]heptanamide:

The reaction and the treatment were conducted in the same manner as in Example 71 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 91-93° C.

IR (KBr) cm⁻¹: 3436, 3213, 3169, 2962, 2929, 1666, 1505, 1152.

¹H-NMR (d₆-DMSO) δ: 1.29 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.31 (6H, d, J=6.8 Hz), 1.40-1.52 (4H, m), 1.60-1.68 (2H, m), 1.85 (2H, quint, J=7.1 Hz), 2.17-2.32 (2H, m), 2.43 (3H, s), 2.47 (3H, s), 3.22 (1H, sept, J=6.8 Hz), 3.35 (2H, t, J=7.1 Hz), 3.56 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 6.93 (1H, s), 7.15 (1H, s), 8.67 (1H, br s).

EIMS m/z (relative intensity): 609 (M⁺; ³⁷Cl), 607 (M⁺; ³⁵Cl), 532 (100).

Example 118 (Compound No. 1303 in Table)

Production of 8-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]octanamide:

The reaction and the treatment were conducted in the same manner as in Example 72 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow oil.

IR (Cap) cm⁻¹: 3242, 2964, 2928, 1668, 1559, 1506, 1148.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.6 Hz), 1.31 (12H, d, J=6.8 Hz), 1.32-1.50 (6H, m), 1.57-1.67 (2H, m), 1.82 (2H, quint, J=7.1 Hz), 2.17-2.27 (2H, m), 2.42 (3H, s), 2.46 (3H, s), 3.21 (1H, sept, J=6.8 Hz), 3.33 (2H, t, J=7.1 Hz), 3.55 (1H, sept, J=6.6 Hz), 3.89 (1H, sept, J=6.8 Hz), 6.91 (1H, s), 7.14 (1H, s), 8.65 (1H, br s).

EIMS m/z (relative intensity): 623 (M⁺: ³⁷Cl), 621 (M⁺: ³⁵Cl), 546 (100).

Example 119 (Compound No. 1304 in Table)

Production of 9-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]nonanamide:

The reaction and the treatment were conducted in the same manner as in Example 73 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzoxazole to obtain the desired compound as a pale yellow oil.

IR (Cap) cm⁻¹: 3249, 2961, 2926, 1667, 1563, 1505.

¹H-NMR (d₆-DMSO) δ: 1.28 (6H, d, J=6.8 Hz), 1.30 (12H, d, J=7.1 Hz), 1.28-1.50 (8H, m), 1.55-1.65 (2H, m), 1.81 (2H, quint, J=7.1 Hz), 2.17-2.27 (2H, m), 2.41 (3H, s), 2.46 (3H, s), 3.21 (1H, sept, J=7.1 Hz), 3.32 (2H, t, J=7.1 Hz), 3.54 (1H, sept, J=6.8 Hz), 3.89 (1H, sept, J=7.1 Hz), 6.91 (1H, s), 7.14 (1H, s), 8.65 (1H, br s).

EIMS m/z (relative intensity): 637 (M^(+:) ³⁷Cl), 635 (M⁺: ³⁵Cl), 560 (100).

Example 120 (Compound No. 1317 in Table)

Production of 2-(7-methansulfonylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 96 except that 2-mercapto-7-methansulfonylbenzoxazole was used instead of 2-mercapto-7-trifluoromethylbenzoxazole to obtain the desired compound as a colorless needle crystal.

Melting point: 159-162° C.

IR (KBr) cm⁻¹: 3449, 3271, 2966, 2928, 1678, 1508, 1315, 1118.

¹H-NMR (CDCl₃) δ: 1.14 (3H, t, J=7.3 Hz), 1.20 (3H, t, J=7.3 Hz), 2.43 (3H, s), 2.82 (2H, q, J=7.3 Hz), 3.01 (2H, q, J=7.3 Hz), 3.27 (2H, s), 4.15 (2H, s), 6.63 (1H, s), 7.49 (1H, t, J=7.9 Hz), 7.83 (1H, dd, J=7.9, 1.2 Hz), 7.90 (1H, dd, J=7.9, 1.2 Hz), 8.17 (1H, br s).

EIMS m/z (relative intensity): 497 (M⁺), 311 (100).

Elemental analysis: as C₂₀H₂₃N₃O₄S₄; Calculated: C, 48.27; H, 4.66; N, 8.44; S, 25.77. Found: C, 48.36; H, 4.66; N, 8.31; S, 25.76.

Example 121 (Compound No. 1327 in Table)

Production of 2-(7-methansulfonylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 74 except that 2-mercapto-7-methansulfonylbenzoxazole was used instead of 2-mercaptobenzothiazole to obtain the desired compound as a pale yellow amorphous.

IR (KBr) cm⁻¹: 3435, 3337, 2965, 2926, 1695, 1506, 1424, 1319, 1117.

¹H-NMR (CDCl₃) δ: 1.16 (6H, d, J=6.8 Hz), 1.21 (6H, d, J=6.8 Hz), 2.42 (3H, s), 3.26 (3H, s), 3.40 (1H, sept, J=6.8 Hz), 3.90 (1H, sept, J=6.8 Hz), 4.15 (2H, s), 6.68 (1H, s), 7.49 (1H, t, J=7.9 Hz), 7.83 (1H, dd, J=7.9, 1.0 Hz), 7.90 (1H, dd, J=7.9, 1.0 Hz), 8.11 (1H, br s).

EIMS m/z (relative intensity): 525 (M⁺), 339 (100).

Example 122 (Compound No. 1341 in Table)

Production of 6-(benzoxasole-2-ylthio)-N-(4-methyl-2-(methylthio)-5-pyridyl)hexanamide:

A methanol (8 mml) solution of 2-dichloro-4-methyl-5-nitropyrimidine (2.0 g, 10.4 mmol) was added dropwise to a methanol (8 ml) solution of sodium thiomethoxide (436 mg, 5.9 mmol) while being cooled with ice, and after the mixture was stirred for 15 hours while raising its temperature to the room temperature, water added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was recrystalized with ethyl acetate-hexan to obtain 1.02 g (yield 98%) of 4-methyl-2-methylthio-5-nitropyridine as a pale-yellow needle crystal.

This nitropyridine (497 mg, 2.7 mmol) was dissolved in a mixed solvent of acetic acid (15 ml) and conc. hydrochloric acid (0.5 ml), and zinc (2.12 g, 32.4 mmol) was added thereto in small portions while being cooled with ice for 5 minutes. After the mixture was stirred for 30 minutes at the room temperature, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate=1:1) to obtain 352 mg (yield 85%) of 5-amino-4-methyl-2-methylthiopyridine as a pale-yellow powdery crystal.

And then the reaction and the treatment were conducted in the same manner as in Example 18 except that 5-amino-4-methyl-2-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

Melting point: 125-127° C.

IR (KBr) cm⁻¹: 3433, 3284, 2930, 1654, 1598.

¹H-NMR (CDCl₃) δ: 1.61 (2H, quint, J=7.4 Hz), 1.83 (2H, quint, J=7.4 Hz), 1.92 (2H, quint, J=7.4 Hz), 2.19 (3H, s), 2.43 (2H, t, J=7.4 Hz), 2.54 (3H, s), 3.33 (2H, t, J=7.4 Hz), 6.92 (1H, br s), 7.03 (1H, s), 7.24 (1H, td, J=7.7, 1.7 Hz), 7.28 (1H, td, J=7.7, 1.7 Hz), 7.43 (1H, dd, J=7.7, 1.7 Hz), 7.57 (1H, dd, J=7.7, 1.7 Hz), 8.57 (1H, s).

EIMS m/z (relative intensity): 401 (M⁺), 69 (100).

Example 123 (Compound No. 1371 in Table)

Production of 6-(benzoxasole-2-ylthio)-N-(5-methylthio-2-pyridyl)hexanamide:

After conc. sulfuric acid (50 ml) was cooled with ice, 30% aqueous solution of hydrogen peroxide (25 ml) was dropped thereto stirring, and then conc. sulfuric acid (50 ml) solution of 2-amino-5-chloropyridine (5.0 g, 38.9 mmol) was dropped thereto further and stirred for 48 hours at the room temperature. The reaction mixture was added into ice and filtered. The residue was recrystallized with ethanol to obtain 4.38 g (yield 71%) of 5-chloro-2-nitoropyriine as a colorless powdery crystal.

A methanol (40 mml) solution of 5-chloro-2-nitropyridine (2.0 g, 12.6 mmol) was added dropwise to a methanol (20 ml) solution of sodium thiomethoxide (1.02 g, 13.9 mmol) while being cooled with ice, and after the mixture was stirred for 13 hours while raising its temperature to the room temperature, water added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was recrystalized with ethyl acetate-hexane to obtain 972 mg (yield 45%) of 5-methylthio-2-nitropyridine.

This nitropyridine (300 mg, 1.8 mmol) was dissolved in a mixed solvent of acetic acid (7 ml) and conc. hydrochloric acid (0.5 ml), and zinc (692 g, 10.6 mmol) was added thereto in small portions while being cooled with ice for 5 minutes. After the mixture was stirred for 30 minutes at the room temperature, the reaction mixture was filtered, and the filtrate was neutralized with an aqueous solution of sodium hydrogencarbonate, and extracted with methylene chloride. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Thereafter, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (eluent-hexane:ethyl acetate=1:1→chloroform:methanol=20:1) to obtain 158 mg (yield 64%) of 2-amino-5-methylthiopyridine as a pale-yellow powdery crystal.

And then the reaction and the treatment were conducted in the same manner as in Example 18 except that 2-amino-5-methylthiopyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

Melting point: 83-85° C.

IR (KBr) cm⁻¹: 3246, 2930, 1684, 1576, 1522.

¹H-NMR (CDCl₃) δ: 1.59 (2H, quint, J=7.4 Hz), 1.81 (2H, quint, J=7.4 Hz), 1.90 (2H, quint, J=7.4 Hz), 2.42 (2H, t, J=7.4 Hz), 2.48 (3H, s), 3.32 (2H, t, J=7.4 Hz), 7.23 (1H, td, J=7.4, 1.4 Hz), 7.28 (1H, td, J=7.4, 1.4 Hz), 7.43 (1H, dd, J=7.4, 1.4 Hz), 7.59 (1H, dd, J=7.4, 1.4 Hz), 7.64 (1H, dd, J=8.6, 2.5 Hz), 7.82 (1H, br s), 8.15 (1H, d, J=8.6 Hz), 8.18 (1H, d, J=2.5 Hz).

EIMS m/z (relative intensity): 387 (M⁺, 100).

Example 124 (Compound No. 1401 in Table)

Production of 6-(benzoxazol-2-ylthio)-N-[2,4,6-tris(methylthio)-5-pyrimidyl]hexanamide:

The reaction and the treatment were conducted in the same manner as in Example 88 except that 4,6-dihydroxy-2-methylthiopyrimidine was used instead of 4,6-dihydroxy-2-methylpyrimidine to obtain the desired compound as a colorless powdery crystal.

Melting point: 149-153° C.

IR (KBr) cm⁻¹: 3448, 3247, 2926, 1667, 1496.

¹H-NMR (CDCl₃) δ: 1.46-1.62 (2H, m), 1.63-1.76 (2H, m), 1.77-1.91 (2H, m), 2.20-2.36 (2H, m), 2.46 (9H, s), 3.36 (2H, t, J=7.1 Hz), 7.22-7.35 (2H, m), 7.51-7.62 (2H, m), 9.02 (1H, br s).

EIMS m/z (relative intensity): 480 (M⁺, 100).

Example 125 (Compound No. 1427 in Table)

Production of 2-(7-methoxycarbonylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 26 except that 2-mercapto-7-methoxycarbonylbenzoxazole was used instead of 2-mercaptobenzoxasole to obtain the desired compound as a colorless needle crystal.

Melting point: 168-169° C.

IR (KBr) cm⁻¹: 3433, 3257, 1727, 1677, 1513, 1297, 1120.

¹H-NMR (CDCl₃) δ: 1.16 (3H, t, J=7.4 Hz), 1.19 (3H, t, J=7.4 Hz), 2.42 (3H, s), 2.80 (2H, q, J=7.4 Hz), 3.03 (2H, q, J=7.4 Hz), 4.00 (3H, s), 4.12 (2H, s), 6.63 (1H, s), 7.38 (1H, dd, J=8.1, 7.8 Hz), 7.80 (1H, dd, J=8.1, 1.2 Hz), 7.92 (1H, dd, J=7.8, 1.2 Hz), 8.48 (1H, br s).

EIMS m/z (relative intensity): 477 (M⁺), 323 (100).

Elemental analysis: as C₂₁H₂₃N₃O₄S₃; Calculated: C, 52.81; H, 4.85; N, 8.80; S, 20.14. Found: C, 52.90; H, 4.91; N, 8.73; S, 20.12.

Example 126 (Compound No. 1428 in Table)

Production of 2-(oxazolo[4,5-b]pyridine-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 49 except that 2-mercaptoxazolo[4,5-b]pyridine was used instead of 2-mercaptobenzoxasole to obtain the desired compound as a colorless crystal.

IR (KBr) cm⁻¹: 3460, 3167, 2972, 1685, 1561.

¹H-NMR (CDCl₃) δ: 1.14 (3H, t, J=7.4 Hz), 1.21 (3H, t, J=7.4 Hz), 2.42 (3H, s), 2.82 (2H, q, J=7.4 Hz), 3.02 (2H, q, J=7.4 Hz), 4.16 (2H, s), 6.62 (1H, s), 7.25 (1H, dd, J=8.3, 5.1 Hz), 7.78 (1H, dd, J=8.3, 1.2 Hz), 8.40 (1H, br s), 8.49 (1H, dd, J=5.1, 1.2 Hz).

EIMS m/z (relative intensity): 420 (M⁺, 100).

Example 127 (Compound No. 1257 in Table)

Production of 2-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 49 except that 5-chloro-7-isopropyl-2-mercapto-4-methylbenzoxazole was used instead of 2-mercaptobenzothiazole to obtain the desired compound as a colorless powdery crystal.

EIMS m/z (relative intensity): 481 (M⁺), 210 (100).

Example 128 (Compound No. 1277 in Table)

Production of 2-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(ethylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 127 except that 3-amino-2,4-bis(isopropylthio)-6-methylpyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

EIMS m/s (relative intensity): 511 (M⁺; ³⁷Cl), 509 (M⁺; ³⁵Cl), 235 (100).

Example 129 (Compound No. 1297 in Table)

Production of 2-(5-chloro-7-isopropyl-4-methylbenzoxazol-2-ylthio)-N-[2,4-bis(isopropylthio)-6-methyl-3-pyridyl]acetamide:

The reaction and the treatment were conducted in the same manner as in Example 127 except that 3-amino-2,4-bis(isopropylthio)-6-methylpyridine was used instead of 3-amino-2,4-bis(methylthio)-6-methylpyridine to obtain the desired compound as a colorless powdery crystal.

EIMS m/z (relative intensity): 539 (M⁺; ³⁷Cl), 537 (M⁺; ³⁵Cl), 223 (100). 

1. Compounds represented by the formula (I)

wherein

represents an optionally substituted divalent residue of benzene, cyclohexane or naphthalene, or a group:

Het represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms; X represents an oxygen atom; Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; and n is an integer of from 2 to 15, or salts or solvates thereof.
 2. The compounds according to claim 1, which are represented by the formula (IA)

wherein

represents an optionally substituted divalent residue of; Py represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms; X represents an oxygen atom; Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; and n is an integer of from 2 to 15; or salts or solvates thereof.
 3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound selected from the compounds represented by the formula (I)

wherein

represents an optionally substituted divalent residue of benzene, cyclohexane or naphthalene, or a group:

Het represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms; X represents an oxygen atom; Y represents —NR—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; and n is an integer of from 2 to 15, or salts or solvates thereof.
 4. The pharmaceutical composition according to claim 3, which is a remedy or a medication for preventing hyperlipemia, arteriosclerosis, cerebrovascular accidents, ischemic heart disease, ischemic intestinal disease or aortic aneurysm.
 5. A method for treating hyperlipemia, arteriosclerosis, cerebrovascular accidents, ischemic heart disease, ischemic intestinal disease or aortic aneurysm by administering to a patient in need of such treatment a compound of the formula (I′)

wherein

represents an optionally substituted divalent residue of benzene, cyclohexane or naphthalene, or a group:

Het represents substituted or unsubstituted pyridyl group; X represents an oxygen atom; Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; and n is an integer of from 1 to 15; or salts or solvates thereof.
 6. The method of claim 5 wherein a compound of formula (I′A) is administered

wherein

represents an optionally substituted divalent residue of benzene; Py represents an optionally substituted pyridyl or pyrimidinyl group; X represents an oxygen atom; Y represents —NR₄—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; n is an integer of from 1 to 15, or salts or solvates thereof.
 7. The method of claim 5 wherein a compound of formula (III′) is administered

wherein, W represents ═CH—, X represents an oxygen atom; Y represents —NR₄— an oxygen atom, a sulfur atom, a sulfoxide or a sulfone; Z represents a single bond; R₁, R₂, and R₃ are the same or different, and each represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a hydroxyl group, a phosphate group, a sulfonamide group, a lower alkylthio group or an optionally substituted amino group, or two of R₁, R₂, and R₃, together form an alkylenedioxide group; R₄ represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group; and n is an integer of from 1 to 15; or salts or solvates thereof.
 8. A method claim 5 wherein a compound represented by formula (I) is administered,

wherein

represents an optionally substituted divalent residue of benzene; Het represents a substituted or unsubstituted pyridyl group; X is an oxygen atom; Y is a sulfur atom; Z is a single bond; n is 1; or salts or solvates thereof.
 9. The compound of claim 1, wherein the Het represents a 2,4-di(alkylthio)-6-methyl-pyridin-3-yl, wherein each alkylthio group has between 1 and 6 carbon atoms.
 10. The compound of claim 2, wherein the Py represents a 2,4-di(alkylthio)-6-methyl-pyridin-3-yl, wherein each alkylthio group has between 1 and 6 carbon atoms.
 11. The pharmaceutical composition of claim 3, wherein the Het represents a 2,4-di(alkylthio)-6-methyl-pyridin-3-yl, wherein each alkylthio group has between 1 and 6 carbon atoms.
 12. The method of claim 5, wherein Het represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms.
 13. The method of claim 8, wherein Py represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms.
 14. The method of claim 8, wherein Het represents a 2,4-disubstituted-6-alkyl-pyridin-3-yl, wherein each substituent is a lower alkyloxy group having between 1 and 6 carbon atoms or a lower alkylthio group having between 1 and 6 carbon atoms. 